Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (96)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Fransen, E.
Right arrow Articles by Willems, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fransen, E.
Right arrow Articles by Willems, P. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics Pages 1625-1632

L1-associated diseases: clinical geneticists divide, molecular geneticists unite
Introduction
Mutations In L1 Are Responsible For HSAS
L1-Associated Diseases
The L1 Cell Adhesion Molecule: A Neuronal Cell Adhesion Molecule Involved In Nervous System Development
   Structural features
   L1 functions
   Binding partners of L1
   Signal transduction
L1 Mutations: An Update
Genetic Heterogeneity
Acknowledgements
References

L1-associated diseases: clinical geneticists divide, molecular geneticists unite

L1-associated diseases: clinical geneticists divide, molecular geneticists unite Erik Fransen, Guy Van Camp, Lieve Vits and Patrick J. Willems*

Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium

Received May 7, 1997

The neuronal cell adhesion molecule L1 (L1CAM) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily and is essential in the development of the nervous system. It is mainly expressed on neurons and Schwann cells, and plays a key role in axon outgrowth and pathfinding through interactions with various extracellular ligands and intracellular second messenger systems. Mutations in L1 are responsible for a wide spectrum of neurologic abnormalities and mental retardation. This spectrum includes X-linked hydrocephalus, MASA syndrome, X-linked complicated spastic paraplegia type 1 and X-linked agenesis of the corpus callosum. These four diseases were initially described as distinct clinical entities with an overlapping clinical spectrum, but can now be lumped into one syndrome caused by mutations in the L1 gene. The main clinical features of this spectrum are Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus, which has led to the acronym CRASH syndrome.

INTRODUCTION

In 1949 Bickers and Adams described a British family with several male sibs that died at birth from congenital hydrocephalus (1 ). Post-mortem examination showed structural brain malformations with narrowing of the aqueduct of Sylvius. As the aqueduct stenosis was assumed to be the cause of hydrocephalus, the syndrome became referred to as Hydrocephalus due to Stenosis of the Acqueduct of Sylvius (HSAS).

The clinical and pathological features of this recessive X-linked condition have been extensively reviewed (2 -5 ). The incidence is generally estimated to be around 1 in 30 000 male births (6 ). In general, patients with X-linked hydrocephalus show a broad spectrum of clinical and neurological abnormalities. The severity of these abnormalities is highly variable, sometimes even within the same family (2 ,7 ). The only obligate feature of HSAS is mental retardation with IQs usually between 20 and 50. Most patients also have spasticity of the lower limbs, which is most likely caused by hypoplasia of the corticospinal tract (5 ). Adducted thumbs (or clasped thumbs) are also found in many cases. Other manifestations of HSAS include a variety of structural brain malformations, among which agenesis or dysgenesis of the corpus callosum or the septum pellucidum.

MUTATIONS IN L1 ARE RESPONSIBLE FOR HSAS

In 1990 we found close linkage of HSAS to polymorphic markers located on the distal part of the long arm of the X-chromosome, in band Xq28 (8 ). Further mapping studies refined the disease locus to a region of 2 Mb, between DXS52 and F8C (9 -11 ). At that time, few genes were known in the Xq28 region. The most interesting candidate gene was the gene encoding L1 (L1 Cell Adhesion Molecule, also referred to as L1CAM), since the L1 protein was known to be involved in the development of the brain (12 ). In 1992, aberrant splicing of the L1 mRNA was reported in a HSAS patient, suggesting that L1 is the HSAS gene (13 ). Definite proof for the involvement of the L1 gene in HSAS was obtained by the finding of two additional L1 mutations in HSAS families: a 1.3 kb duplication near the 3' end of the L1 open reading frame (14 ) and a missense mutation disrupting a disulfide bridge (15 ).

L1-ASSOCIATED DISEASES

HSAS shows considerable clinical overlap with a number of X-linked conditions, including MASA syndrome (Mental Retardation, Aphasia, Shuffling gait, Adducted thumbs), complicated Spastic Paraplegia type 1 (SP-1), Agenesis of Corpus Callosum (ACC) and Mental Retardation with Clasped Thumbs (MR-CT) (16 -19 ). Linkage analysis had assigned the disease loci for MASA syndrome (20 ), SP-1 (17 ) and MR-CT (19 ) to Xq28, the L1 region. Several of these phenotypes occur in a single family (21 -23 ). These data led to the hypothesis that these conditions represent pleiotropic effects of mutations in a single gene (9 ), which was confirmed when L1 mutations were found in all these conditions (24 -27 ). This proved that HSAS, MASA, SP-1, ACC and MR-CT are not separate conditions, but rather represent overlapping clinical spectra due to mutations in the L1 gene. Since a separation between the different L1-associated diseases no longer made sense, and most typical symptoms include Corpus callosum agenesis, Retardation, Adducted thumbs, Shuffling gait and Hydrocephalus, the acronym CRASH syndrome was proposed to refer to the clinical spectrum of diseases caused by an L1 mutation (28 ).

Additional conditions that might be caused by L1 mutations are MRX3 and PH. MRX3 is a form of aspecific mental retardation linked to Xq28 (29 ,30 ). So far, no evidence for L1 mutations has been reported. Periventricular Heterotopia (PH), which was recently mapped to Xq28 (31 ), is caused by a migration defect during cerebral cortical development, and affected patients suffer from several types of epilepsy. L1 was suggested as a candidate gene, but no evidence of L1 mutations has yet been found (C.A.Walsh, personal communication).

CRASH syndrome covers a very wide and variable clinical spectrum, that is limited to mental retardation alone in some patients. Hence, the possibility of an L1 mutation should be considered in mentally retarded males without additional symptoms. Therefore, mutations in L1 might be a more frequent cause of mental retardation than can be derived from the literature.

THE L1 CELL ADHESION MOLECULE: A NEURONAL CELL ADHESION MOLECULE INVOLVED IN NERVOUS SYSTEM DEVELOPMENT

Structural features

L1 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily (IgSF). In human, the mature protein has 1256 amino acids with an extracellular part consisting of six Ig-like domains and five fibronectin type III-like domains, a single-pass transmembrane domain and a short cytoplasmic C-terminal tail (32 ,33 ). L1 homologues have been discovered in: rat (NILE), mouse (l1), Drosophila (Neuroglian), Manduca (Neuroglian), chicken (NgCAM), zebrafish (L1.1- and L1.2-CAM), Fugu and goldfish [reviewed in (34 )]. The domain structure of L1 is characteristic for a subgroup of the IgSF which is now referred to as the L1 subfamily of adhesion molecules (35 ). It comprises a number of evolutionary related neural cell adhesion molecules, all implicated in the development of the nervous system, including L1 (and its homologues in other species), Bravo/NrCAM, neurofascin/ABGP and CHL1 (34 ,36 ). The Ig domains of L1 were originally described as belonging to the C2 set of Ig-like domains. However, comparison with other proteins revealed that the Ig domains of L1 make a close match to the sequence profile from a novel structural set of the IgSF, referred to as the I set (37 ,38 ).

In humans, the gene encoding L1 has 28 exons. An alternative splicing variant lacking exons 2 and 27 has been described (39 ,40 ). This isoform seems to be restricted to non-neural cells, although the functional significance remains to be elucidated (41 ). The alternatively spliced exon 27, located in the cytoplasmic domain, is conserved among many vertebrate members of the L1 family, which underlines its functional importance (34 ).

L1 functions

Cell adhesion molecules play critical roles in mediating the interaction between a cell and its environment [reviewed in (42 )]. L1 expression was originally thought to be limited to the nervous system, particularly on outgrowing axons and growth cones of postmitotic nerve cells in the central (CNS) and peripheral (PNS) nervous system, and on Schwann cells in the PNS. During nervous system development, L1 plays a role in adhesion between neurons and between neurons and Schwann cells (12 ,43 ,44 ), in myelination (45 ), in axon outgrowth and pathfinding (46 ,47 ), axon fasciculation (48 ,49 ), growth cone morphology (50 ,51 ) and neuronal migration (52 ,53 ). In addition, L1 is involved in regeneration of damaged nerve tissue (54 ), and has been implicated in long-term memory formation (55 ) and the establishment of long-term potentiation in the hippocampus (56 ).


Figure 1. The L1 protein and mutations in CRASH syndrome. The signal peptide, the six Ig domains, five fibronectin domains, the transmembrane and the cytoplasmic domain are indicated on the left. The functional sites and alternatively spliced exons are denoted on the right. Missense point mutations are denoted by a filled dot (-). Deletions which do not alter the reading frame are represented by a line parallel with the molecule. Mutations causing a frameshift are schematically represented by an open dot ([circle]). In-frame nonsense mutations are denoted by an asterisk (J) The intron mutations which are very likely to cause alternative splicing, but that are not yet fully characterized on the mRNA level, are not shown. The numbers of the mutations are the same as in Table 1.

Recently, non-neural L1 expression of an alternatively spliced L1 lacking exons 2 and 27 has been described in the male urogenital tract (57 ), in the intestinal crypt cells (58 ) and in cells of hematopoetic origin (59 ). The function of L1 in these tissues, however, is unclear.

Table 1 . Overview of L1 mutations in CRASH syndromea
Number Exon/intron Domain cDNA change Type of mutation Protein change Reference mutation Reference patient
1 E 1 s.p. G26 -> C missense W9S 89 11
2 E 1 s.p. 52 ins C insertion 1 bp FS 18 90  
3 I 1 s.p. 76+1 g -> t splice site ? 91  
4 I 4 Ig 1 400+5 g -> a splice site FS 108 92 7
5 E 4 Ig 1 G361 -> A missense G121S 89  
6 E 5 Ig 2 404 CC -> A complex FS 135 Antwerp, unpublished  
7 I 5 Ig 2 523+26 del 31 splice site ? Antwerp, unpublished  
8 I 5 Ig 2 524-2 a -> c splice site ? Antwerp, unpublished  
9 E 6 Ig 2 T536 -> G missense I179S 93 22
10 E 6 Ig 2 C550 -> T missense R184W 94
11 E 6 Ig 2 G551 -> A missense R184Q 25 95
12 E 6 Ig 2 A581 -> G missense Y194C 90
13 E 6 Ig 2 C630 -> G missense H210Q 24,25 23
14 E 6 Ig 2 644 del G deletion 1 bp FS 215 94 3
15 E 7 Ig 3 712 ins 4 insertion 4 bp FS 239 94  
16 E 7 Ig 3 C719 -> T missense P240L 90  
17 E 7 Ig 3 G791 -> A missense C264Y 15 11
18 E 7 Ig 3 G803 -> A missense G268D Antwerp, unpublished  
19 I 7 Ig 3 807-6g -> a splice site FS 268 96  
20 E 8 Ig 3 G828 -> A nonsense W276X 90  
21 E 8 Ig 3 841 del 5 deletion 5 bp FS 281 97  
22 E 8 Ig 3 G925 -> A missense E309K 89  
  E 8 Ig 3 G925 -> A missense E309K Antwerp, unpublished 19
23 E 8 Ig 3 955 del G deletion 1 bp FS 319 90  
24 E 9 Ig 3 C998 -> G missense P333R Sue Forrest, pers.comm.  
25 E 9 Ig 4 G1108 -> A missense G370R 93 98
26 I 9 Ig 4 1124-1 g -> a splice site ? Antwerp, unpublished  
27 I 9 Ig 4 1124-1 g -> c splice site ? Antwerp, unpublished  
28 E 10 Ig 4 T1172 -> C missense L391P Antwerp, unpublished  
29 E 10 Ig 4 1198 del A deletion 1 bp FS 400 94  
30 E 10 Ig 4 1248 del T deletion 1 bp FS 416 94 99
31 I 10 Ig 4 ? splice site [Delta]E10 100  
32 I 10 Ig 4 1267+1 g -> a splice site ? 94  
  I 10 Ig 4 1267+1 g -> a splice site ? Antwerp, unpublished  
33 I 10 Ig 4 1267+4 a -> t splice site [Delta]E10 89  
34 E 11 Ig 5 C1277 -> A missense A426D Antwerp, unpublished  
35 E 11 Ig 5 1296 del 4 deletion 4 bp FS 433 Antwerp, unpublished  
36 E 11 Ig 5 1316 del 15 in-frame deletion 439 del 5 AA 96  
37 E 11 Ig 5 C1318 -> T nonsense Q440X 88  
38 E 11 Ig 5 G1354 -> A missense G452R 25  
39 E 12 Ig 5 T1445 -> C missense L482P 88  
40 E 12 Ig 5 C1453 -> T nonsense R485X 25  
41 E 13 Ig 6 1576 del 3 in-frame deletion [Delta]S526 88  
42 E 13 Ig 6 T1624 -> C missense S542P 88  
43 E 13 Ig 6 C1672 -> T nonsense R558X 96  
44 E 14 Ig 6 C1756 -> T nonsense Q586X 89  
45 E 14 Ig 6 1780 del A deletion 1 bp FS 594 94  
46 E 14 Ig 6 G1792 -> A missense D598N 24 20
47 E 15 Fn 1 G1895 -> C missense R632P 27 18
48 E 16 Fn 1 A1963 -> G missense K655E 101  

Table 1. continued
Number Exon/intron Domain cDNA change Type of mutation Protein change Reference mutation Reference patient
49 E 17 Fn 2 2153 del C deletion 1 bp FS718 Antwerp, unpublished  
50 E 18 Fn 2 T2222 -> C missense M741T 88  
51 E 18 Fn 2 G2254 -> A missense V752M 88  
52 E 18 Fn 2 G2262 -> A nonsense W754X 96  
53 E 18 Fn 2 G2302 -> A missense V768I 88  
54 E 18 Fn 2 G2302 -> T missense V768F 89  
55 E 18 Fn 2 A2351 -> G missense Y784C 96  
56 E 18 Fn 2 A2374 -> GG complex FS 791 96  
57 E 18 Fn 2 2430 del CT deletion 2 bp FS 810 Antwerp, unpublished  
58

 I 18

 Fn 2

 2432-19 a -> c

 splice site

 811 ins 23 AAb
[Delta]E 19b		 13

 11
59 E 20 Fn 3 C2701 -> T nonsense R901X 96  
60 E 21 Fn 4 ? splice site [Delta]E 21 100  
61 E 21 Fn 4 2805 del 39 in-frame deletion 936 del 13 AA 96  
62 E 21 Fn 4 C2822 -> T missense P941L 89  
63 E 22 Fn 4 2885 del G deletion 1 bp FS 962 25  
  E 22 Fn 4 2885 del G deletion 1 bp FS 962 Antwerp, unpublished  
64 E 23 Fn 5 3088 del A deletion 1 bp FS 1030 85 87
65 E 23 Fn 5 C3124 -> T nonsense Q1042X 88  
66 E 24 Fn 5 A3209 -> G missense Y1070C 89 11
67 I 24 ? 3322+2 t -> c splice site ? 96  
68 E 25 Fn 5 3323 del G deletion 1 bp FS 1108 Antwerp, unpublished  
69 E 25 Cytopl. 3453 del 4 nonsense Y1151X Antwerp, unpublished  
  E 25 Cytopl. 3453 del 4 nonsense Y1151X Antwerp, unpublished  
70 E 26 Cytopl. 3489 del TG deletion 2 bp FS 1164 25 17
71 I 26 Cytopl. 3531-12 g -> a splice site ? 89 102
72 I 27 -> 28 Cytopl. 3543 del 2 kb large deletion del 1181 -> end 24 103
73 E 28 Cytopl. C3581 -> T missense S1194L 26 21
74 E 28 Cytopl. 3543 dpl 125 large duplication FS 1223 14 2
75 E 28 Cytopl. T3685 -> C missense Y1229H Antwerp, unpublished  
aAn updated table of L1 mutations is available electronically at the L1CAM mutation homepage (http://hgins.uia.ac.be/dnalab/l1/)
bmRNA studies indicated the presence of two aberrantly spliced mRNA species, besides the normally spliced mRNA.s.p., signal peptide; FS, Frameshift; bp, basepair; Cytopl., Cytoplasmic domain.

Binding partners of L1

As most IgSF members, L1 protein has homophilic interactions with an L1 protein on the membrane of an adjacent cell (60 ). The homophilic binding site has been mapped to the second Ig domain (Fig. 1 ) (61 ). Heterophilic interactions have been described with cell adhesion molecules belonging to the IgSF, including axonin-1/TAG-1 (49 ,62 ), F3/F11 (63 ) and DM-GRASP (64 ). Furthermore, L1 interacts with the neuronal chondroitin sulfate proteoglycans neurocan and phosphacan (65 ,66 ). Apart from interactions with other cells (trans-interactions), cis-interactions have been reported with NCAM (67 ) and the heat-stable antigen nectadrin (HSA, murine CD24) (68 ,69 ). Recently, evidence has emerged that L1 is involved in integrin-mediated cell-cell and cell-matrix interactions, both in neuronal cells, tumor cells and cells of haematopoetic lineage [reviewed in (70 )]. Human [alpha]v[beta]3 integrin (vitronectin receptor) (71 ,72 ) and murine fibronectin receptor [alpha]5[beta]1 (VLA-5) (73 ) bind to L1 via the RGD sequence in the sixth Ig domain of L1, and may induce haptotactic cell migration and activation of immune responses.


Figure 2. Position of the various mutations dispersed over the L1 gene. Exons are drawn as grey boxes, introns as lines. The exons but not the introns are drawn to scale. The position of the different domains with regard to the genomic structure is outlined. The mutations, numbered according to Table 1, are indicated by vertical arrows.

Signal transduction

Several signal transducing pathways are involved in passing extracellular interactions of L1 to the intracellular machinery of the cell. Antibody-induced stimulation of L1 leads to changes in intracellular pH, Ca2+ and inositol phosphates, depending on the cell type (74 ,75 ). Doherty and asssociates postulated that L1 signal transduction occurs via cis-activation of the Fibroblast Growth Factor Receptor (FGFR) through an amino acid motif shared between FGFR and L1 (76 -78 ). Maness and co-workers obtained evidence that the non-receptor tyrosine kinase pp60c-src is part of the L1 signaling cascade, as L1-mediated neurite outgrowth is diminished in src-minus neurons (79 ). A number of kinase activities, co-precipitating with L1 immunoprecipitates, phosphorylate the cytoplasmic domain at distinct Ser residues. Phosphorylation may be a way for modulation of L1 signal transducing activity (49 ,74 ,80 ,81 ). The L1 cytoplasmic domain is anchored to the actin cytoskeleton via an interaction with ankyrin, a shared feature between many neuronal cell adhesion molecules (69 ,82 ,83 ).

L1 MUTATIONS: AN UPDATE

Up to now, 75 different L1 mutations have been described in 79 different CRASH families. These mutations are summarized in Table 1 , and depicted in Figures 1 and 2 . Most L1 mutations are private mutations that occur in only one family. Frequently occurring L1 mutations have not been found, and only four mutations were reported in two independent families: (mutations 22, 32, 63 and 69). The mutations are dispersed throughout the entire L1 gene and have been found in each domain. No indication for mutation hot spots has been found, although the regions around exons 6, 10, 11 and 18 are relatively rich in mutations. The mutational spectrum includes two gross rearrangements, 14 splice site mutations (including one branch point signal mutation), 30 missense mutations, nine nonsense mutations, three in-frame deletions and 17 mutations leading to a frameshift (13 small deletions, two small insertions and two complex mutations). Only two of the mutations (mutations 72 and 74) are detectable by Southern blot analysis. Mutation screening of the L1 gene has been greatly facilitated by the availability of the complete genomic sequence of L1 (EMBL accession no. Z29373) (84 ).

As the list of L1 mutations is still growing, we constructed the L1 mutation Web Page (http://hgins.uia.ac.be/dnalab/l1/), a WWW page with information about L1, including a continuously updated overview of all L1 mutations (85 ).

Two cases of somatic and germline mosaicism have been reported [mutations 47 (27 ) and 64 (86 )]. The occurrence of germline mosaicism is a potential caveat in the genetic counseling of families with CRASH syndrome.

GENETIC HETEROGENEITY

Up to now, no conclusive evidence for genetic heterogeneity of X-linked hydrocephalus (HSAS) has been found although many families have been described. Nevertheless, two families with HSAS were reported in which the L1 gene was excluded as the disease gene by linkage analysis. In the first family linkage to the L1 region in Xq28 was initially excluded (87 ), but afterwards an L1 mutation was identified in this family (85 ). Screening of the entire family for the presence of the mutation revealed that the mutation had occurred de novo in a female, who was a somatic and germline mosaic for the mutation. This mosaicism had led to a discordant segregation of the Xq28 markers and the disease. Also in a small German HSAS family (Family 12) comprising an affected male and his affected nephew, linkage to Xq28 has been excluded by us and others (9 ,88 ), based upon the observation that one apparently normal brother had inherited the same Xq28 haplotype as the two patients. Recently, an L1 amino acid substitution (V768I) was identified in both the two patients and the apparently normal brother (88 ). The authors concluded that the V768I substitution is a rare non-pathogenic polymorphism, and not the disease-causing mutation, and that HSAS is caused by a gene other than L1 in this family. In our opinion, however, it cannot be excluded that the V768I substitution in L1 is the disease-causing mutation in this family for two reasons. First, non-pathogenic amino acid substitutions have never been found in L1. Second, mildly affected CRASH patients have been reported previously (3 ,23 ) and the apparently healthy sib might be mildly affected, as he refused any clinical and IQ testing. In conclusion, convincing evidence for genetic heterogeneity of X-linked hydrocephalus has yet to be presented.

ACKNOWLEDGEMENTS

We are indebted to C.Schrander-Stumpel, A.Munnich, S.Lyonnet, J.J.A.Holden, D.Chitayat, J.-J.Cassiman and M.Sagi for referral of patients. We thank Vance Lemmon for critically reviewing the manuscript. This study was supported in part by grants from the FWO (Belgian Fund for Scientific Research) and the French AFM (Association Française contre les Myopathies) to P.J.W. and a concerted action from the University of Antwerp to G.V.C. and P.J.W.

REFERENCES

1 Bickers,D.S. and Adams,R.D. (1949) Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus. Brain 72, 246-262.

2 Willems,P.J., Brouwer,O.F., Dijkstra,I. and Wilmink,J. (1987) X-linked hydrocephalus. Am. J. Med. Genet. 27, 921-928. MEDLINE Abstract

3 Schrander-Stumpel,C., Höweler,C., Jones,M., Sommer,A., Stevens,C., Tinschert,S., Israel,J. and Fryns,J.P. (1995) Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): clinical review with six additional families. Am. J. Med. Genet. 57, 107-116. MEDLINE Abstract

4 Yamasaki,M., Arita,N., Hiraga,S., Izumoto,S., Morimoto,K., Nakatani,S., Fujitani,K., Sato,N. and Hayakawa,T. (1995) A clinical and neuroradiological study of X-linked hydrocephalus in Japan. J. Neurosurg. 83, 50-55. MEDLINE Abstract

5 Kenwrick,S., Jouet,M. and Donnai,D. (1996) X linked hydrocephalus and MASA syndrome. J. Med. Genet. 33, 59-65. MEDLINE Abstract

6 Halliday,J., Chow,C.W., Wallace,D. and Danks,D.M. (1986) X-linked hydrocephalus: A survey of a 20 year period in Victoria, Australia. J. Med. Genet. 23, 23-31. MEDLINE Abstract

7 Serville,F., Lyonnet,S., Pelet,A., Reynaud,M., Louial,C., Munnich,A. and Le Merrer,M. (1992) X-linked hydrocephalus: clinical heterogeneity at a single gene locus. Eur. J. Pediatr. 151, 515-518. MEDLINE Abstract

8 Willems,P.J., Dijkstra,I., Van der Auwera,B.J., Vits,L., Coucke,P., Raeymakers,P., Van Broeckhoven,C., Consalez,G.G., Freeman,S.B., Warren,S.T., Brouwer,O.F., Brunner,H.G., Renier,W.O., Van Elsen,A.F. and Dumon,J.E. (1990) Assignment of X-linked hydrocephalus to Xq28 by linkage analysis. Genomics 8, 367-370. MEDLINE Abstract

9 Willems,P.J., Vits,L., Raymakers,P., Beuten,J., Coucke,P., Holden,J.J.A., Van Broeckhoven,C., Warren,S.T., Sagi,M., Robinson,D., Dennis,N., Friedman,K.S., Magnay,D., Lyonnet,S., White,B.N., Wittwer,B.H., Aylsworth,A.S. and Reicke,S. (1992) Further localization of X-linked hydrocephalus in the chromosomal region Xq28. Am. J. Hum. Genet. 51, 307-315. MEDLINE Abstract

10 Lyonnet,S., Pelet,A., Royer,G., Delrieu,O., Serville,F., Le Marec,B., Gruensteudel,A., Pfeiffer,R.A., Briard,M.L., Dubay,C., Hors-Cayla,M.C., Le Merrer,M. and Munnich,A. (1992) The gene for X-linked hydrocephalus maps to Xq28, distal to DXS52. Genomics 14, 508-510. MEDLINE Abstract

11 Jouet,M., Feldman,E., Yates,J., Donnai,D., Paterson,J., Siggers,D. and Kenwrick,S. (1993) Refining the genetic localisation of the gene for X-linked hydrocephalus within Xq28. J. Med. Genet. 30, 214-217. MEDLINE Abstract

12 Rathjen,F.G. and Schachner,M. (1984) Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 3, 1-10.

13 Rosenthal,A., Jouet,M. and Kenwrick,S. (1992) Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nature Genet. 2, 107-112. MEDLINE Abstract

14 Van Camp,G., Vits,L., Coucke,P., Lyonnet,S., Schrander-Stumpel,C., Darby,J., Holden,J.J.A., Munnich,A. and Willems,P.J. (1993) A duplication in the L1CAM gene associated with X-linked hydrocephalus. Nature Genet. 4, 421-425. MEDLINE Abstract

15 Jouet,M., Rosenthal,A., MacFarlane,J.R., Kenwrick,S. and Donnai,D. (1993) A missense mutation confirms the L1 defect in X-linked hydrocephalus. Nature Genet. 4, 331 MEDLINE Abstract

16 Bianchine,J.W. and Lewis,R.C. (1974) The MASA syndrome: a new hereditary mental retardation syndrome. Clin. Genet. 5, 298-306. MEDLINE Abstract

17 Kenwrick,S., Ionanescu,V., Ionanescu,G., Searby,C., King,A., Dubowitz,M. and Davies,K.E. (1986) Linkage studies of X-linked recessive spastic paraplegia using DNA probes. Hum. Genet. 73, 264-266. MEDLINE Abstract

18 Kaplan,P. (1983) X-linked recessive inheritance of agenesis of the corpus callosum. J. Med. Genet. 20, 122-124. MEDLINE Abstract

19 Straussberg,R. (1991) X-linked mental retardation with bilateral clasped thumbs: report of another affected family. Clin. Genet. 40, 337-341. MEDLINE Abstract

20 Winter,R.M., Davies,K.E., Bell,M.V., Huson,S.M. and Patterson,M.N. (1989) MASA syndrome: further clinical delineation and chromosomal localisation. Hum. Genet. 83, 367-370.

21 Schrander-Stumpel,C., Legius,E., Fryns,J.P. and Cassiman,J.J. (1990) MASA syndrome: new clinical features and linkage analysis using DNA probes. J. Med. Genet. 27, 688-692. MEDLINE Abstract

22 Fryns,J.P., Spaepen,A., Cassiman,J.J. and Van den Berghe,H. (1991) X-linked complicated spastic paraplegia, MASA syndrome and X-linked hydrocephaly due to congenital stenosis of the aqueduct of Sylvius: a variable expression of the same mutation at Xq28. J. Med. Genet. 28, 429-431. MEDLINE Abstract

23 Boyd,E., Schwartz,C.E., Schroer,R.J., May,M.M., Shapiro,S.D., Arena,F., Lubs,H.A. and Stevenson,R.E. (1993) Agenesis of the corpus callosum associated with MASA syndrome. Clin. Dysmorphol. 2, 332-341. MEDLINE Abstract

24 Vits,L., Van Camp,G., Coucke,P., Fransen,E., De Boulle,K., Reyniers,E., Korn,B., Poustka,A., Wilson,G.N., Schrander-Stumpel,C., Winter,R.M., Schwartz,C.E. and Willems,P.J. (1994) MASA syndrome is due to mutations in the L1CAM gene. Nature Genet. 7, 408-413. MEDLINE Abstract

25 Jouet,M., Rosenthal,A., Armstrong,G., MacFarlane,J.R., Stevenson,R., Paterson,J., Matzenberg,A., Ionanescu,V., Temple,K. and Kenwrick,S. (1994) X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nature Genet. 7, 402-407.

26 Fransen,E., Schrander-Stumpel,C., Vits,L., Coucke,P., Van Camp,G. and Willems,P.J. (1994) X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene. Hum. Mol. Genet. 3, 2255-2256. MEDLINE Abstract

27 Vits,L., Chitayat,D., Van Camp,G., Holden,J.J.A., Fransen,E. and Willems,P.J. (1997) Somatic and germline mosaicism for an L1 mutation causing agenesis of the corpus callosum. Hum. Mutat. In press.

28 Fransen,E., Lemmon,V., Van Camp,G., Vits,L., Coucke,P. and Willems,P.J. (1995) CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. Eur. J. Hum. Genet. 3, 273-284. MEDLINE Abstract

29 Gedeon,A., Kerr,B., Mulley,J. and Turner,G. (1991) Localisation of the MRX3 gene for non-specific X-linked mental retardation. J. Med. Genet. 28, 372-377. MEDLINE Abstract

30 Nordström,A.M., Penttinen,M. and von Koskull,H. (1992) Linkage to Xq28 in a family with nonspecific X-linked mental retardation. Hum. Genet. 90, 263-266. MEDLINE Abstract

31 Eksioglu,Y.Z., Scheffer,I.E., Cardenas,P., Knoll,J., DiMario,F., Ramsby,G., Berg,M., Kamuro,K., Berkovic,S.F., Duyk,G.M., Parisi,J., Huttenlocher,P.R. and Walsh,C.A. (1996) Periventricular Heterotopia: An X-linked dominant epilepsy locus causing aberrant cerebral cortical development. Neuron 16, 77-87. MEDLINE Abstract

32 Moos,M., Tacke,R., Scherer,H., Teplow,D., Fruh,K. and Schachner,M. (1988) Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domain similar to fibronectin. Nature 334, 701-702. MEDLINE Abstract

33 Hlavin,M.L. and Lemmon,V. (1991) Molecular structure and functonal testing of human L1CAM: an interspecies comparison. Genomics 11, 416-423. MEDLINE Abstract

34 Hortsch,M. (1996) The L1 family of neural cell adhesion molecules - Old proteins performing new tricks. Neuron 17, 587-593. MEDLINE Abstract

35 Grumet,M., Mauro,V., Burgoon,M.P., Edelman,G.M. and Cunningham,B.A. (1991) Structure of a new nervous system glycoprotein Nr-CAM and its relationship to subgroups of neural adhesion molecules. J. Cell Biol. 113, 1399-1412. MEDLINE Abstract

36 Holm,J., Hillenbrand,R., Bartsch,U., Moos,M., Lübbert,H., Montag,D. and Schachner,M. (1996) Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules. Eur. J. Neurosci. 8, 1613-1629.

37 Harpaz,Y. and Cothia,C. (1994) Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J. Mol. Biol. 238, 528-539. MEDLINE Abstract

38 Bateman,A., Jouet,M., MacFarlane,J.R., Du,J.-S., Kenwrick,S. and Cothia,C. (1996) Outline structures of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders. EMBO J. 15, 6050-6059. MEDLINE Abstract

39 Reid,R.A. and Hemperly,J.J. (1992) Variants of human L1-cell adhesion molecule arise through alternate splicing of RNA. J. Mol. Neurosci. 3, 127-135. MEDLINE Abstract

40 Jouet,M., Rosenthal,A. and Kenwrick,S. (1995) Exon 2 of the gene for neural cell adhesion molecule L1 is alternatively spliced in B cells. Mol. Brain Res. 30, 378-380. MEDLINE Abstract

41 Takeda,Y., Asou,H., Murakami,Y., Miura,M., Kobayashi,M. and Uyemura, K. (1996) A nonneural isoform of cell adhesion molecule L1: tissue-specific expression and functional analysis. J. Neurochem. 66, 2338-2349. MEDLINE Abstract

42 Tessier-Lavigne,M. and Goodman,C.S. (1996) The molecular biology of axon guidance. Science 274, 1123-1133. MEDLINE Abstract

43 Faissner,A., Kruse,J., Nieke,J. and Schachner,M. (1984) Expression of neural cell adhesion molecule L1 during development, in neurological mutants and in the peripheral nervous system. Dev. Brain Res. 15, 69-82.

44 Persohn,E. and Schachner,M. (1987) Immunoelectron microscopic localization of the neural cell adhesion molecules L1 and N-CAM during postnatal development of the mouse cerebellum. J. Cell Biol. 105, 569-576. MEDLINE Abstract

45 Wood,P.M., Schachner,M. and Bunge,R.P. (1990) Inhibition of schwann cell myelination in vitro by antibody to the L1 adhesion molecule. J. Neurosci. 10, 3636-3645.

46 Fisher,G., Künemund,V. and Schachner,M. (1986) Neurite outgrowth patterns in cerebral microexplant cultures are affected by antibodies to the cell surface glycoprotein L1. J. Neurosci. 6, 605-612.

47 Lagenaur,C. and Lemmon,V. (1987) An L1-like molecule, the 8D9 antigen, is a potent substrate for neurite extension. Proc. Natl. Acad. Sci. USA 84, 7753-7757. MEDLINE Abstract

48 Chang,S., Rathjen,F.G. and Raper,J.A. (1987) Extension of neurites on axons is impaired by antibodies against specific neural cell surface glycoproteins. J. Cell Biol. 104, 355-362. MEDLINE Abstract

49 Kunz,S., Riegler,U., Kunz,B. and Sonderegger,P. (1996) Intracellular signaling is changed after clustering of the neural cell adhesion molecules axonin-1 and NgCAM during neurite fasciculation. J. Cell Biol. 135, 253-267. MEDLINE Abstract

50 Payne,H.R., Burden-Gulley,S.M. and Lemmon,V. (1992) Modulation of growth cone morphology by substrate-bound adhesion molecules. Cell Motil. Cytoskel. 21, 65-73.

51 Burden-Gulley,S.M., Payne,H.R. and Lemmon,V. (1995) Growth cones are actively influenced by substrate-bound adhesion molecules. J. Neurosci. 15, 4370-4381. MEDLINE Abstract

52 Lindner,J., Rathjen,F.G. and Schachner,M. (1983) L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum. Nature 305, 427-430. MEDLINE Abstract

53 Asou,H., Miura,M., Kobayashi,M., Uyemura,K. and Itoh,K. (1992) Cell adhesion molecule L1 guides cell migration in primary reaggregation culture of mouse cerebellar cells. Neurosci. Lett. 144, 221-224. MEDLINE Abstract

54 Martini,R. and Schachner,M. (1988) Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, Myelin-associated Glycoprotein) in regenerating adult mouse sciatic nerve. J. Cell Biol. 106, 1735-1746.

55 Rose,S.P.R. (1995) Cell-adhesion molecules, glucocorticoids and long-term-memory formation. Trends Neurosci. 18, 502-506.

56 Luhti,A., Laurent,J.P., Figurov,A., Muller,D. and Schachner,M. (1994) Hippocampal long-term potentiating and neural cell adhesion molecules L1 and NCAM. Nature 372, 777-779.

57 Kujat,R., Miragall,F., Krause,D., Dermietzel,R. and Wrobel,K.-H. (1995) Immunolocalization of neural cell adhesion molecule L1 in non-proliferating epithelial cell of the male urogenital tract. Histochemistry 103, 311-321.

58 Thor,G., Probstmeier,R. and Schachner,M. (1987) Characterization of the cell adhesion molecules L1, N-CAM and J1 in the mouse intestine. EMBO J. 6, 2581-2586. MEDLINE Abstract

59 Kowitz,A., Kadmon,G., Eckert,M., Schirrmacher,V., Schachner,M. and Altevogt,P. (1992) Expression and function of the neural cell adhesion molecule L1 in mouse leukocytes. Eur. J. Immunol. 22, 1199-1205. MEDLINE Abstract

60 Lemmon,V., Farr,K.L. and Lagenaur,C. (1989) L1-mediated axon outgrowth occurs via a homophilic binding mechanism. Neuron 2, 1597-1603. MEDLINE Abstract

61 Zhao,X. and Siu,C.-H. (1995) Colocalization of the homophilic binding site and the neuritogenic activity of the cell adhesion molecule L1 to its second Ig-like domain. J. Biol. Chem. 270, 29413-29421. MEDLINE Abstract

62 Kuhn,T.B., Stoeckli,E.T., Condrau,M.A., Rathjen,F.G. and Sonderegger,P. (1991) Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4). J. Cell Biol. 115, 1113-1126.

63 Brümmendorf,T., Hubert,M., Treubert,U., Leuscher,R., Tarnok,A. and Rathjen,F.G. (1993) The axonal recognition molecule F11 is a multifunctional protein: Specific domains mediate interactions with NgCAM and restrictin. Neuron 10, 711-727. MEDLINE Abstract

64 DeBernardo,A.P. and Chang,S. (1996) Heterophilic interactions of DM-GRASP: GRASP-NgCAM interactions involved in neurite extension. J. Cell Biol. 133, 657-666. MEDLINE Abstract

65 Milev,P., Friedlander,D.R., Sakuri,T., Karthikeyan,L., Flad,M., Margolis,R.K., Grumet,M. and Margolis,R.U. (1994) Interactions of the chondroitin sulfate proteoglycan phosphacan, the extracellular domain of a receptor-type protein tyrosine phosphatase, with neurons, glia and neural cell adhesion molecules. J. Cell Biol. 127, 1703-1715. MEDLINE Abstract

66 Friedlander,D.R., Milev,P., Karthikeyan,L., Margolis,R.K., Margolis,R.U. and Grumet,M. (1994) The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules NgCAM/L1/NILe and N-CAM, and inhibits neuronal adhesion and neurite outgrowth. J. Cell Biol. 125, 669-680. MEDLINE Abstract

67 Kadmon,G., Kowitz,A., Altevogt,P. and Schachner,M. (1990) The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions. J. Cell Biol. 110, 193-208. MEDLINE Abstract

68 Kadmon,G., von Bohlen und Halbach,F., Horstkorte,R., Eckert,M., Altevogt,P. and Schachner,M. (1995) Evidence for cis interaction and cooperative signaling by the heat-stable antigen nectadrin (murine CD24) and the cell adhesion molecule L1 in neurons. Eur. J. Neurosci. 7, 993-1004.

69 Sammar,M., Aigner,S. and Altevogt,P. (1997) Heat-stable antigen (mouse CD24) in the brain: dual but distinct interaction with P-selectin and L1. Biochim. Biophys. Acta 1337, 287-294.

70 Kadmon,G. and Altevogt,P. (1997) The cell adhesion molecule L1: species- and cell-type-dependent multiple binding mechanisms. Differentiation 61, 143-150. MEDLINE Abstract

71 Montgomery,A., Becker,J., Siu,C.-H., Lemmon,V., Cheresh,D., Pancook,J., Zhao,X. and Reisfeld,R. (1996) Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin [alpha]v[beta]3. J. Cell Biol. 132, 475-485. MEDLINE Abstract

72 Ebeling,O., Duczmal,A., Aigner,S., Geiger,C., Schöllhammer,S., Kemshead,J.T., Möller,P., Schwartz-Albiez,R. and Altevogt,P. (1996) L1 cell adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to [alpha]v[beta]3 integrin. Eur. J. Immunol. 26, 2508-2516. MEDLINE Abstract

73 Ruppert,M., Aigner,S., Hubbe,M., Yagita,H. and Altevogt,P. (1995) The L1 adhesion molecule is a cellular ligand for VLA-5. J. Cell Biol. 6, 1881-1891.

74 Schuch,U., Lohse,M.J. and Schachner,M. (1989) Neural cell adhesion molecules influence second messenger systems. Neuron 3, 13-20. MEDLINE Abstract

75 von Bohlen und Halbach,F., Taylor,J. and Schachner,M. (1992) Cell type-specific effects of the neural cell adhesion molecules L1 and N-CAM on diverse second messenger systems. Eur. J. Neurosci. 4, 896-909.

76 Williams,E.J., Furness,J., Walsh,F.S. and Doherty,P. (1994) Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM and N-cadherin. Neuron 13, 583-594. MEDLINE Abstract

77 Williams,E.J., Mittal,B., Walsh,F.S. and Doherty,P. (1995) FGF inhibits neurite outgrowth over monolayers of astrocytes and fibroblasts expressing transfected cell adhesion molecules. J. Cell Sci. 108, 3523-3530. MEDLINE Abstract

78 Safell,J.L., Williams,E.J., Mason,I.J., Walsh,F.S. and Doherty,P. (1997) Expression of a dominant negative FGF receptor inhibits axonal growth and FGF receptor phosphorylation stimulated by CAMs. Neuron 18, 231-242.

79 Ignelzi,M.A., Miller,D.R., Soriano,P. and Maness,P.F. (1994) Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1. Neuron 12, 873-884. MEDLINE Abstract

80 Wong,E., Schaefer,A., Landreth,G. and Lemmon,V. (1996) Casein kinase II phosphorylates the neural cell adhesion molecule L1. J. Neurochem. 66, 779-786. MEDLINE Abstract

81 Wong,E., Schaefer,A., Landreth,G. and Lemmon,V. (1996) Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1. J. Biol. Chem. 271, 18217-18223. MEDLINE Abstract

82 Davis,J.Q., McLaughlin,T. and Bennet,V. (1993) Ankyrin-binding proteins related to nervous system cell adhesion molecules: Candidates to provide transmembrane and intercellular connections in adult brain. J. Cell Biol. 121, 121-133. MEDLINE Abstract

83 Davis,J.Q. and Bennet,V. (1994) Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules. J. Biol. Chem. 269, 27163-27166. MEDLINE Abstract

84 Rosenthal, A., Coutelle, O. and Drescher, B. (1994) Genomic sequence and structure of the human gene for the neural cell adhesion molecule L1/HSAS locus. EMBL accession no Z29373

85 Van Camp,G., Fransen,E., Vits,L., Raes,R. and Willems,P.J. (1996) A locus-specific mutation database for the neural cell adhesion molecule L1. Hum. Mutat. 8, 391. MEDLINE Abstract

86 Jouet,M., Strain,L., Bonthron,D. and Kenwrick,S. (1996) Discordant segregation of Xq28 markers and a mutation in the L1 gene in a family with X linked hydrocephalus. J. Med. Genet. 33, 218-250.

87 Strain,L., Gosden,C.M., Brock,D.J.H. and Bonthron,D.T. (1994) Genetic heterogeneity in X-linked hydrocephalus: linkage to markers within Xq27.3. Am. J. Hum. Genet. 54, 236-243. MEDLINE Abstract

88 Gu,S.-M., Orth,U., Zankl,M., Schröder,J. and Gal,A. (1996) Molecular Analysis of the L1CAM gene in patients with X-linked hydrocephalus demonstrates eight novel mutations and suggests non-allelic genetic heterogeneity of the trait. Am. J. Med. Genet. In press.

89 Jouet,M., Moncla,A., Paterson,J., McKeown,C., Fryer,A., Carpenter,N., Holmberg,E., Wadelius,C. and Kenwrick,S. (1995) New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome. Am. J. Hum. Genet. 56, 1304-1314. MEDLINE Abstract

90 Gu,S.-M., Orth,U., Veske,A., Enders,H., Klunder,K., Schlosser,M., Engel,W., Schwinger,E. and Gal,A. (1996) Five novel mutations in the L1CAM gene in families with X linked hydrocephalus. J. Med. Genet. 33, 103-106. MEDLINE Abstract

91 Jouet,M. and Kenwrick,S. (1995) Gene analysis of L1 neural cell adhesion molecule in prenatal diagnosis of hydrocephalus. Lancet 345, 161-162. MEDLINE Abstract

92 Coucke,P., Vits,L., Van Camp,G., Serville,F., Lyonnet,S., Kenwrick,S., Rosenthal,A., Wehnert,M., Munnich,A. and Willems,P.J. (1994) Indentification of a 5' splice site mutation in intron 4 of the L1CAM gene in an X-linked hydrocephalus family. Hum. Mol. Genet. 3, 671-673. MEDLINE Abstract

93 Ruiz,J.C., Cuppens,H., Legius,E., Fryns,J.P., Glover,T.W., Marynen,P. and Cassiman,J.J. (1995) Mutations in L1CAM in two families with X-linked complicated spastic paraplegia, MASA syndrome and HSAS. J. Med. Genet. 32, 549-552. MEDLINE Abstract

94 Fransen,E., Vits,L., Van Camp,G. and Willems,P.J. (1996) The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule. Am. J. Med. Genet. 64, 73-77. MEDLINE Abstract

95 Edwards,J.H., Norman,R.M. and Roberts,J.M. (1961) Sex-linked hydrocephalus: report of a family with 15 affected members. Arch. Dis. Child 36, 481-485.

96 MacFarlane,J.R., Du,J.-S., Pepys,M.E., Ramsden,S., Donnai,D., Charlton,R., Garrett,C., Tolmie,J., Yates,J.R.W., Berry,C., Goudie,D., Moncla,A., Lunt,P., Hodgson,S., Jouet,M. and Kenwrick,S. (1997) Nine novel L1 CAM mutations in families with X-linked hydrocephalus. Hum. Mutat. In press.

97 Takechi,T., Tohyama,J., Kurashige,T., Maruta,K., Uyemura,K., Ohi,T., Matsukura,S. and Sakuragawa,N. (1996) A deletion of five nucleotides in the L1CAM gene in a Japanese family with X-linked hydrocephalus. Hum. Genet. 97, 353-356. MEDLINE Abstract

98 Kaepernick,L.A., Legius,E., Higgins,J.V. and Kapur,S. (1994) Clinical aspects of MASA syndrome in a large family, including expressing females. Clin. Genet. 45, 181-185.

99 Váradi,V., Csécsei,K., Szeifert,G.T., Tóth,Z. and Papp,Z. (1987) Prenatal diagnosis of X-linked hydrocephalus without aqueductal stenosis. J. Med. Genet. 24, 207-209. MEDLINE Abstract

100 Forrest,S.M., Rosenthal,A. and Balnaves,M.E. (1994) Mutation detection in X-linked hydrocephalus. Am. J. Hum. Genet. 55,1279 abstract.

101 Izumoto,S., Yamasaki,M., Arita,N., Hiraga,S., Ohnishi,T., Fujitani,K., Sakoda,S. and Hayakawa,T. (1996) A new mutation of the L1CAM gene in an X-linked hydrocephalus family. Child's Nerv. Syst. 12, 742-747.

102 Yeatman,G.W. (1984) Mental retardation-clasped thumb syndrome. Am. J. Med. Genet. 17, 339-344. MEDLINE Abstract

103 Macias,V.R., Day,D.W., King,T.E. and Wilson,G.N. (1992) Clasped-thumb mental retardation (MASA) syndrome: confirmation of linkage to Xq28. Am. J. Med. Genet. 43, 408-414.

* To whom correspondence should be addressed. Tel: +32 3 820 25 66; Fax: +32 3 820 25 66; Email: dnalab@uia.ua.ac.be

-->
This page is maintained by OUP admin. Last updated Fri Sep 12 18:09:23 BST 1997. Part of the OUP Journals World Wide Web service. Copyright Oxford University Press, 1997


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
K. Nagaraj, L. V. Kristiansen, A. Skrzynski, C. Castiella, L. Garcia-Alonso, and M. Hortsch
Pathogenic human L1-CAM mutations reduce the adhesion-dependent activation of EGFR
Hum. Mol. Genet., October 15, 2009; 18(20): 3822 - 3831.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb. Perspect. Biol.Home page
N. Giagtzoglou, C. V. Ly, and H. J. Bellen
Cell Adhesion, the Backbone of the Synapse: "Vertebrate" and "Invertebrate" Perspectives
Cold Spring Harb Perspect Biol, October 1, 2009; 1(4): a003079 - a003079.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Shtutman, E. Levina, P. Ohouo, M. Baig, and I. B. Roninson
Cell Adhesion Molecule L1 Disrupts E-Cadherin-Containing Adherens Junctions and Increases Scattering and Motility of MCF7 Breast Carcinoma Cells
Cancer Res., December 1, 2006; 66(23): 11370 - 11380.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Cheng, K. Itoh, and V. Lemmon
L1-Mediated Branching Is Regulated by Two Ezrin-Radixin-Moesin (ERM)-Binding Sites, the RSLE Region and a Novel Juxtamembrane ERM-Binding Region
J. Neurosci., January 12, 2005; 25(2): 395 - 403.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. D. Malhotra, V. Thyagarajan, C. Chen, and L. L. Isom
Tyrosine-phosphorylated and Nonphosphorylated Sodium Channel {beta}1 Subunits Are Differentially Localized in Cardiac Myocytes
J. Biol. Chem., September 24, 2004; 279(39): 40748 - 40754.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
A.E. Wiencken-Barger, J. Mavity-Hudson, U. Bartsch, M. Schachner, and V.A. Casagrande
The Role of L1 in Axon Pathfinding and Fasciculation
Cereb Cortex, February 1, 2004; 14(2): 121 - 131.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. A. Greenberg
Linking acquired neurodevelopmental disorders to defects in cell adhesion
PNAS, July 8, 2003; 100(14): 8043 - 8044.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. G. M. Frints, P. Marynen, D. Hartmann, J.-P. Fryns, J. Steyaert, M. Schachner, B. Rolf, K. Craessaerts, A. Snellinx, K. Hollanders, et al.
CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior
Hum. Mol. Genet., July 1, 2003; 12(13): 1463 - 1474.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Buhusi, B. R. Midkiff, A. M. Gates, M. Richter, M. Schachner, and P. F. Maness
Close Homolog of L1 Is an Enhancer of Integrin-mediated Cell Migration
J. Biol. Chem., June 27, 2003; 278(27): 25024 - 25031.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Montag-Sallaz, M. Schachner, and D. Montag
Misguided Axonal Projections, Neural Cell Adhesion Molecule 180 mRNA Upregulation, and Altered Behavior in Mice Deficient for the Close Homolog of L1
Mol. Cell. Biol., November 15, 2002; 22(22): 7967 - 7981.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
C. B. Dobson, F. Villagra, G. J. Clowry, M. Smith, S. Kenwrick, D. Donnai, S. Miller, and J. A. Eyre
Abnormal corticospinal function but normal axonal guidance in human L1CAM mutations
Brain, December 1, 2001; 124(12): 2393 - 2406.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. K. Needham, K. Thelen, and P. F. Maness
Cytoplasmic Domain Mutations of the L1 Cell Adhesion Molecule Reduce L1-Ankyrin Interactions
J. Neurosci., March 1, 2001; 21(5): 1490 - 1500.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. M. Jenkins, K. Kizhatil, N. R. Kramarcy, A. Sen, R. Sealock, and V. Bennett
FIGQY phosphorylation defines discrete populations of L1 cell adhesion molecules at sites of cell-cell contact and in migrating neurons
J. Cell Sci., January 11, 2001; 114(21): 3823 - 3835.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-L. Wang, M. Kutsche, G. DiSciullo, M. Schachner, and S. A. Bogen
Selective Malformation of the Splenic White Pulp Border in L1-Deficient Mice
J. Immunol., September 1, 2000; 165(5): 2465 - 2473.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Silletti, F. Mei, D. Sheppard, and A. M.P. Montgomery
Plasmin-Sensitive Dibasic Sequences in the Third Fibronectin-like Domain of L1-Cell Adhesion Molecule (Cam) Facilitate Homomultimerization and Concomitant Integrin Recruitment
J. Cell Biol., June 26, 2000; 149(7): 1485 - 1502.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R.-S. Schmid, W. M. Pruitt, and P. F. Maness
A MAP Kinase-Signaling Pathway Mediates Neurite Outgrowth on L1 and Requires Src-Dependent Endocytosis
J. Neurosci., June 1, 2000; 20(11): 4177 - 4188.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Kenwrick, A. Watkins, and E. D. Angelis
Neural cell recognition molecule L1: relating biological complexity to human disease mutations
Hum. Mol. Genet., April 1, 2000; 9(6): 879 - 886.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
L. Sztriha, P. Frossard, R. M.W. Hofstra, E. Verlind, and M. Nork
Novel Missense Mutation in the L1 Gene in a Child With Corpus Callosum Agenesis, Retardation, Adducted Thumbs, Spastic Paraparesis, and Hydrocephalus
J Child Neurol, April 1, 2000; 15(4): 239 - 243.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
G. P. Demyanenko, A. Y. Tsai, and P. F. Maness
Abnormalities in Neuronal Process Extension, Hippocampal Development, and the Ventricular System of L1 Knockout Mice
J. Neurosci., June 15, 1999; 19(12): 4907 - 4920.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Marg, P. Sirim, F. Spaltmann, A. Plagge, G. Kauselmann, F. Buck, F. G. Rathjen, and T. Brummendorf
Neurotractin, A Novel Neurite Outgrowth-promoting Ig-like Protein that Interacts with CEPU-1 and LAMP
J. Cell Biol., May 17, 1999; 145(4): 865 - 876.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
H. Debiec, E. I. Christensen, and P. M. Ronco
The Cell Adhesion Molecule L1 Is Developmentally Regulated in the Renal Epithelium and Is Involved in Kidney Branching Morphogenesis
J. Cell Biol., December 28, 1998; 143(7): 2067 - 2079.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
P. Scotland, D. Zhou, H. Benveniste, and V. Bennett
Nervous System Defects of AnkyrinB (-/-) Mice Suggest Functional Overlap between the Cell Adhesion Molecule L1 and 440-kD AnkyrinB in Premyelinated Axons
J. Cell Biol., November 30, 1998; 143(5): 1305 - 1315.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
H. Volkmer, U. Zacharias, U. Norenberg, and F. G. Rathjen
Dissection of Complex Molecular Interactions of Neurofascin with Axonin-1, F11, and Tenascin-R, Which Promote Attachment and Neurite Formation of Tectal Cells
J. Cell Biol., August 24, 1998; 142(4): 1083 - 1093.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (96)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Fransen, E.
Right arrow Articles by Willems, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fransen, E.
Right arrow Articles by Willems, P. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?