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 (46)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Wenstrup, R. J.
Right arrow Articles by Cole, W. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wenstrup, R. J.
Right arrow Articles by Cole, W. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics Pages 1733-1737
A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro[alpha]1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I)
Introduction
Results
Discussion
Materials And Methods
   Clinical information
   Genotyping
   Heteroduplex analysis
   Mutation analysis
Acknowledgements
References

A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro[alpha]1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I)

A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro [alpha] 1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I) Richard J. Wenstrup*, Gregory T. Langland, Marcia C. Willing1, Vinita N. D'Souza2 and William G. Cole2

Division of Human Genetics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA, 1Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, IA, USA and 2The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada

Received May 12, 1996; Revised and Accepted August 19, 1996

Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: [alpha]1(V)2[alpha]2(V) or [alpha]1(V)[alpha]2(V)[alpha]3(V). We report that genomic polymorphisms at the pro[alpha]1(V) gene (COL5A1) locus cosegregated with the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three generation family. Affected family members, who had classical features including joint hyperextensibility, fragile skin, and widened, atrophic scars, were heterozygous for a 4 bp deletion at positions from +3 to +6 of intron 65, which resulted in removal of exon 65 sequences from processed mRNAs. Since exon 65 encodes 78 residues of the carboxyl propeptide, the expected result of this mutation is reduced efficiency in incorporating mutant pro[alpha]1(V) chains into type V collagen molecules and reduced type V collagen synthesis. These studies indicate that heterozygous mutations in COL5A1 can result in EDS type I. However, linkage studies in other EDS I families indicate the disorder is heterogeneous; linkage to both COL5A1 and COL5A2 was excluded in two other families with EDS I while a fourth family was concordant for linkage to COL5A1 (Z = 2.11; [theta] = 0.00).

INTRODUCTION

The Ehlers-Danlos syndromes (EDS) are a group of inherited disorders characterized by laxity and weakness of dermis, ligaments, blood vessels and fetal membranes. All forms of EDS for which the molecular basis is well established are the result of mutations that code for fibrillar collagen genes or for enzymes that catalyze intracellular or extracellular post-translational modifications of fibrillar collagens (reviewed in refs 1 -4 ). EDS type VI is due to deficiency in lysyl hydroxylase as a result of recessive mutations in its gene (3 ,5 ,6 ), EDS type VII is due to either recessive mutations in the gene for type I collagen N-proteinase (7 ) or to dominant mutations that affect the N-peptidase cleavage site in pro[alpha]1(I) or pro[alpha]2(I) chains, and EDS type IV is due to mutations in the gene for the pro[alpha]1(III) chain of type III collagen (COL3A1).

The genetic basis for EDS type I (EDS I), the gravis form, and type II (EDS II), a milder variant has been the subject of recent investigational interest. EDS I is characterized by joint laxity, hyperextensibility of skin, widened, atrophic scars and autosomal dominant inheritance. EDS II differs from EDS I more in degree than in kind: it is clinically similar to EDS I except that the skin is less fragile, scars are more normal in appearance, and prematurity of affected fetuses is far less common. For both EDS I and II, genetic abnormalities that result in abnormal type I collagen fibril structure have been suspected. Ultrastructural studies of skin in some EDS I and II patients have detected abnormally thick type I collagen fibrils (8 ; reviewed in 9 ), and fiber bundles are abnormally small. However, linkage studies have excluded type I collagen genes themselves as the genetic defect in some EDS I and II families (10 ,11 ).

There has been recent interest in type V collagen as a candidate molecule in EDS (12 ). Type V and type I collagen molecules form heterotypic collagen fibrils (12 ), and there is both in vitro (13 ) and in vivo (12 ) evidence that type V collagen may regulate fibril diameter. Transgenic mice that synthesized type V molecules containing mutant pro[alpha]2(V) chains that lack the N-proteinase cleavage site exhibited some features of EDS, including dermal fragility and skin distensibility, and had electron microscopic evidence of collagen fibril disruption (14 ). Nicholls et al. (15 ) have reported preliminary evidence of type V collagen abnormalities in two isolated individuals with features of EDS, and Loughlin and coworkers have recently reported linkage of EDS II to the COL5A1 locus (16 ). A single patient with EDS and hypermelanosis of Ito had a balanced translocation with breakpoints at Xq21.1 and 9q34, and the latter breakpoint was shown by Toriello et al. (17 ) to interrupt COL5A1 and result in haploinsufficiency of pro[alpha]1(V) chains. In this report we demonstrate that an exon skipping mutation in the carboxyl propeptide region of the pro[alpha]1(V) chain of type V collagen cosegregated with EDS I in one family and a second was also concordant for linkage, indicating that [alpha]1(V) chains normally play an important role in the structure and function of connective tissues containing type V collagen.

RESULTS

Figure 1 shows the results of segregation analysis at the COL5A1 locus in one family (Family A) with EDS I. A locus haplotype was generated from three markers: an imperfect SSR within intron 17 of COL5A1 (18 ) and two adjacent genomic markers on chromosome 9q. D9S114 is ~1-3 cM centromeric to COL5A1, and D9S67 is ~4.4 cM telomeric to COL5A1. The family shown in Figure 1 was concordant for linkage. For the intragenic SSR alone, a lod score of 1.20 at [theta] of 0.00 was calculated. A second family (Family B) was concordant for linkage to COL5A1 as well (Z = 2.11; [theta] = 0.00). Linkage at COL5A1 was excluded in two other EDS I families (Families C and D) by a recombination at the intragenic repeat polymorphism and was confirmed with at least one of the flanking markers. For the latter two families, linkage to COL5A2 was also excluded by the finding of one (Family C) or two (Family D) recombinations of a pentanucleotide repeat polymorphism in intron 25 of COL3A1. Tiller et al. (19 ) found no recombination between COL5A2 and the COL3A1 intragenic repeat (Z = 9.93; [theta] = 0.00). In addition, one family with EDS II that was previously shown to be discordant for linkage to COL5A1 (18 ) was also discordant for linkage to COL5A2.


Figure 1. Cosegregation of EDS I with COL5A1 intragenic and flanking chromosome 9 markers (top) and with heteroduplexes generated by misalignment of complementary DNAs from mutant and normal alleles generated by PCR amplification (bottom) in Family A. Open circles/squares in the pedigree indicate unaffected status, closed circles/squares indicate affected status. Allele designations of polymorphic markers are by size in base-pairs of the PCR products. Primers and conditions used for heteroduplex analysis are described in Materials and Methods.

To determine whether concordance for linkage at COL5A1 in Family A was due to a mutation in the coding sequence of COL5A1, pro[alpha]1(V) cDNAs were synthesized from total cellular RNA harvested from cultured dermal fibroblasts explanted from the family's proband. PCR-amplification of cDNAs and subsequent agarose gel electrophoresis yielded a normal 1006 bp cDNA segment that encodes most of the carboxyl-propeptide of the pro[alpha]1(V) chain as well as an abnormal 772 bp product (Fig. 2 ) (20 ,21 ) (see Materials and Methods). The PCR product with the predicted 1006 bp size contained the normal sequence (data not shown) while the shorter product lacked the 234 bp sequence normally encoded by exon 65 (20 -22 ) (Fig. 3 ).


Figure 2. [alpha]1(V) cDNA-PCR products from cultured dermal fibroblasts. Lane 1, DNA blank; lane 2, control; lane 3, proband. The product sizes are indicated and the primers and PCR conditions are described in Materials and Methods.


Figure 3. Sequence of the 772 bp cDNA-PCR product from the proband. The nucleotide and amino acid sequences and the exon assignments are shown. The cDNA sequence reaction was performed using a sense primer and reflects opposite strand. The gel is reversed to show coding sequence rather than opposite strand sequence.

Since the deleted segment from processed RNAs coincided precisely with the published coding sequence of a single exon, genomic sequences adjacent to exon 65 were examined for mutations that might lead to exon skipping. PCR-amplification and sequencing of the 3' splice junction of exon 65 showed that the patient was heterozygous for the loss of four nucleotides, GAGT, corresponding to the +3 to +6 positions in intron 65 (Fig. 4 ). At position +11, a C rather than the reported G was observed in control samples (22 ). The sequence of the 5' splice junction of intron 64 was normal (data not shown).

To confirm that the GAGT deletion at position +3 to +6 in intron 65 was the cause of the EDS phenotype in all affected individuals from Family A, a 135 bp genomic segment that spanned the junction between exon 65 and intron 65 was examined in family members by PCR-heteroduplex analysis (Fig. 1 ). Heteroduplexes resulting from renaturation of misaligned complementary strands comigrated with the 200 bp molecular marker in samples from all three affected family members and from none of the four at-risk offspring who were studied.


Figure 4. Genomic DNA sequences from the junction of exon 65 and intron 65 in the proband and control. The exon sequences are in upper case while intron sequences are in lower case. In the proband, intron 65 contained a double sequence. The sequence from the proband's normal allele is listed on the left and the box encloses the four nucleotides that are missing from the mutant allele.

DISCUSSION

EDS I co-segregated with the gene coding for pro[alpha]1(V) collagen chains (COL5A1) in two families. In two others linkage was excluded at both COL5A1 and COL5A2 loci. Affected individuals in one of the families concordant for linkage to COL5A1 were heterozygous for a 4 bp deletion at positions +3 to +6 of intron 65 of COL5A1, causing deletion of the 234 base pairs of exon 65 in processed mRNAs for pro[alpha]1(V) chains. The mutation, which is in-frame, predicts a pro[alpha]1(V) chain in which the carboxyl propeptide is shortened by 78 amino acids. The deleted segment contains two of the eight highly conserved cysteine residues that are thought to participate in disulfhydryl bonds and facilitate chain association during molecular assembly (20 ,21 ).

The data presented in this report indicate that the EDS I clinical phenotype is caused by a mutation of the pro[alpha]1(V) gene of type V collagen in some families. The fact that EDS II has also been linked to COL5A1 (16 ) is indicative that EDS types I and II constitute a clinical and molecular spectrum. For example, the clinical features of affected members of the EDS II family shown by Loughlin et al. (16 ) to be linked to COL5A1 are not dissimilar to those of affected individuals in the EDS I family described in this report. Whether or not EDS types I and II are considered a single entity, they must still be genetically heterogeneous. We have excluded linkage to both COL5A1 and COL5A2 in two EDS I families and one EDS II family, and heterogeneity is suggested by other workers as well (15 ,16 ). We were unable to make meaningful clinical distinctions between EDS I families that are concordant with linkage to COL5A1 and those for which both COL5A1 and COL5A2 have been excluded. It is possible that mutations in the presumptive COL5A3 gene (23 ,24 ) may be found in some of those families while in others, genetic studies may help identify mutations in other extracellular matrix molecules.

MATERIALS AND METHODS

Clinical information

The minimal diagnostic features for EDS I used for this study included segregation consistent with autosomal dominant inheritance, generalized joint laxity fulfilling Beighton's criteria (reviewed in 3 ), hyperextensible skin having a velvety texture and a doughy consistency, and by the presence of widened, atrophic scars. Extensive periodontal disease as might be expected in EDS VIII was absent. The criteria used to distinguish between EDS I and EDS II was the presence (EDS I) or absence (EDS II) of widened, atrophic scars (3 ). Clinical information on the EDS II family has already been reported (18 ).Family A. The proband is a 40 year old white female with a life-long history of easy bruisibility and cutaneous fragility. The proband's physical examination (by M.C.W.) is remarkable for soft, velvety, hyperelastic skin, which has a doughy consistency. The skin over the elbows, knees, hands and feet is wrinkled and redundant. Numerous wide, atrophic scars, some of which are violaceous in appearance, are seen over the anterior aspect of both knees and tibias. There is mild generalized joint hypermobility which primarily affects the large joints. The proband's first daughter was born at 28 weeks gestation by Caesarean section, after premature rupture of membranes. She also has features consistent with EDS I, with joint hypermobility being more pronounced than that observed in her mother. Family B. The proband is a 38 year old white male with a history of multiple joint dislocations, easy bruisability, and scarring with minimal trauma. Physical examination (by M.C.W.) was remarkable for generalized joint hyperextensibility, soft, doughy hyperelastic skin, extensive wrinkling over the knees, and wrinkling and molluscoid tumors over the elbows. Broad, atrophic scars were present on the face, and there were wide- spread hypertrophic hemosiderotic scars over the anterior aspect of both tibias. Clinical diagnosis was EDS I.Family C. The proband was a 46 year old woman who presented with a history of multiple dislocations of the thumb and left shoulder, easy bruising and prolonged wound healing. Of her five pregnancies, three were at least 6 weeks premature: two single gestations with affected offspring, and one with dizygous twins discordant for EDS. Physical examination of the proband (by R.J.W.) revealed generalized joint hyperextensibility, soft, doughy hyperelastic skin, moderately atrophic scars, with a moderate amount of hemosiderotic scarring over both tibias, and molluscoid tumors over the elbows. Two affected offspring of the proband present more severe `cigarette paper' scars. Clinical diagnosis was EDS I.Family D. The proband was an 18 year female who required surgical correction (by W.G.C.) for hallux valgus. Physical examination revealed generalized joint laxity and paper thin scars over her forehead and anterior tibia. Clinical diagnosis was EDS I.

Genotyping

DNA was extracted either from whole blood or primary skin fibroblasts using standard techniques. PCR was performed in a 10 [mu]l volume containing 30 ng DNA, 5 ng each primer for either D9S67 or D9S114 (Research Genetics, Huntington AL), 10 mM Tris-HCl pH = 8.3, 1.5 mM MgCl2, 50 mM KCl, 0.3 U Taq polymerase (Gibco-BRL), 200 [mu]M dATP, dGTP, dTTP and 2.5 [mu]M dCTP. [[alpha]-32P]dCTP (NEN Du Pont, 3000 Ci/mmol, 10 [mu]Ci/[mu]l) (0.35 [mu]Ci) was used to label the reactions which were performed in a Perkin-Elmer 9600. After denaturation at 94oC for 3 min, 27 cycles were performed, each cycle consisting of 94oC for 30 s, 55oC for 75 s, and 72oC for 15 s. The last extension step was 6 min. Stop solution (10 [mu]l) was added and the samples were heated for 10 min at 80oC. Aliquots (2.5 [mu]l) of each sample were loaded onto a 7% polyacrylamide/8 M urea sequencing gel. Labeled products were detected by autoradiography for 2-48 h using Kodak X-omat XAR film. Autoradiograms were scored by two investigators independently. Linkage to COL5A2 was tested by analysis of pentanucleotide repeats in intron 25 of COL3A1 which is within 35 kb of COL5A2 (19 ).

Heteroduplex analysis

PCR was performed with 500 ng of genomic DNA using 50 ng each of the following primers: (5'-GCCACGGGCAGCTACGACAA-3') and (5-AGGGGTGCTGGGCGCGGCGC-3). After denaturation at 94oC for 1 min, 35 cycles were performed each consisting of 94oC for 20 s, 55oC for 30 s, and 72oC for 45 s. The final extension was at 72oC for 5 min. An aliquot (10 [mu]l) of the PCR reaction was loaded onto a 10% non denaturing polyacrylamide gel. It was then silver stained using a commercially available kit according to the manufacturer's instructions (BioRad, Inc., Hercules, CA).

Mutation analysis

Fibroblasts were grown to confluence in cultures supplemented with ascorbate. Total cellular RNA was extracted using the Trizol reagent (Gibco BRL) and cDNA was prepared from 2.5 [mu]g total cellular RNA using an oligo-dT primer (Gibco BRL) in a 20 [mu]l reaction. The forward primer (i), 5'-CAGGGTATCACTGGTCCTTC-3' and the reverse primer (ii), 5'-AGGTACGAGGTTGCTCTCGG-3', were used to amplify a 1006 bp cDNA product from nucleotides 4552 to 5557 relative to the start site of translation (20 ,21 ). This product extended from exon 58 within the triple helical domain to the 3'-untranslated domain. The PCR reaction included 1 [mu]l cDNA, 2.5 ng/[mu]l of each primer, 0.25 mM dNTPs, 0.05 U/[mu]l Taq polymerase and buffer (10*: 200 mM Tris-HCl, pH 8.8, containing 100 mM (NH4)2SO4, 100 mM KCl, 20 mM MgSO4, 1% Triton X-100, 1 mg/ml BSA). The DNA was denatured at 94oC for 1 min. PCR was undertaken for 35 cycles using denaturation at 94oC for 20 s, annealing at 55oC for 30 s and extension at 72oC for 45 s. In the final cycle, extension was undertaken for 5 min. The PCR products were resolved by electrophoresis on 1% low melting agarose, purified and separately sequenced using primer (ii). As the cDNA findings suggested the loss of exon 65 sequences, exon 65 and its boundaries were amplified using the forward primer (iii) 5'-GCCACGGGCAGCTACGACAA-3' (exon 65) and the reverse primer (iv) 5'-AGGGGTGCTGGGCGCGGCGC-3' (intron 65) under the previous conditions (22 ). The PCR product of 135 bp was resolved on a 1.5% low melting point agarose gel, purified and sequenced using primer (iv). The boundary between intron 64 and exon 65 was also examined. The proband's genomic DNA was amplified using the forward primer (v) 5'-TGCTGAGCCCCAACACCCCT-3' from intron 64 and the reverse primer (vi) 5'-ACTGACTGGTAGCAGTGGTA-3' from exon 65 (21 ). The PCR product was gel purified and sequenced using primer (vi).

ACKNOWLEDGEMENTS

This work was supported by a grant from the Lucille Markey Trust, a grant from the Trustees of the Cincinnati Children's Hospital Research Foundation (to R.J.W.), by the Medical Research Council of Canada, the Research Institute of the Hospital for Sick Children, and the Samuel Lunenfeld Charitable Foundation (to W.G.C.) and by a Carver Clinician Scientist Award (to M.C.W.)

REFERENCES

1 Barabas, A.P., (1987) Heterogenity of the Ehlers-Danlos syndrome: description of three clinical types and a hypothesis to explain the basic defect. Br. Med. J. 2, 612-613.

2 Steinmann, B., Royce, P.M., and Superti-Furga, A. (1993). The Ehlers-Danlos syndrome. In Royce,P.M. and Steinmann,B. (eds), Connective Tissue and its Heritable Disorders. Wiley-Liss, NY. pp 351-408.

3 Beighton, P. (1992). The Ehlers-Danlos Syndromes. In Beighton,P. (ed.), McKusick's Heritable Disorders of Connective Tissue. Mosby, St Louis. MO. pp 189-251.

4 Byers, P.H. (1995). Disorders of collagen biosynthesis and structure. In Schriver,C.R. Beaudet,A.L. Sly,W.S. and Valle,D. (eds), The Metabolic Basis of Inherited Diseases. McGraw-Hill, New York, NY. pp 4029-4078.

5 Pinnell, S.R., Krane, S.M., Densora, J.E. and Glimcher, M.J. (1972) A heritable disorder of connective tissue: hydroxylysine-deficient collagen disease. N. Engl. J. Med. 286, 1013-1020. MEDLINE Abstract

6 Ha, V.T., Marshall, M.K., Elsas, L.J., Pinnell, S.R. and Yeowell, H.N. (1994) A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. J. Clin. Invest. 93, 1716-1721. MEDLINE Abstract

7 Lapiere, C.M. and Nusgens, B.V. (1993) Ehlers-Danlos type vii-C, or human dermatosparaxis. the offspring of a union between basic and clinical research [editorial comment]. Arch. Dermatol. 129, 1316-1319. MEDLINE Abstract

8 Vogel, A., Holbrook, K.A., Steinmann, B., Gitzelmann, R. and Byers, P.H. (1979) Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome. Lab. Investig. 40, 201-206.

9 Holbrook, K.A. and Byers, P.H., (1979) Skin is a window on heritable disorders of connective tissue. J. Med. Genet. 34, 105-121.

10 Wordsworth, B.P., Ogilvie, D.J. and Sykes, B.C. (1991) Segregation analysis of the structural genes of the major fibrillar collagens provides further evidence of molecular heterogeneity in type II Ehlers-Danlos syndrome. Br. J. Rheumatol. 30, 173-177. MEDLINE Abstract

11 Sokolov, B.P., Prytkov, A.N., Tromp, G., Knowlton, R.G. and Prockop, D.J. (1991) Exclusion of COL1A1, COL1A2, and COL3A1 genes as candidate genes for Ehlers-Danlos syndrome type I in one large family. Hum. Genet. 88, 125-129. MEDLINE Abstract

12 Francomano, C.A., (1995) Key role for a minor collagen. Nature Genet. 9, 6-8. MEDLINE Abstract

13 Birk, D.E., Fitch, M., Babiarz, J.P., Doane, K.J. and Linsenmayer, T.F. (1990) Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. J. Cell Sci. 95, 649-657. MEDLINE Abstract

14 Andrikopoulos, K., Liu, X., Keene, D.R., Jaenisch, R. and Ramirez, F. (1995) Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly. Nature Genet. 9, 31-36. MEDLINE Abstract

15 Nicholl, A.C., McCarron, S., Narcisi, P. and Pope, F.M. (1994) Molecular abnormalities in type V collagen in two patients with Ehlers-Danlos syndrome (EDS). Am. J. Hum. Genet. 55S, A233-A230.

16 Loughlin, J., Irven, C., Hardwick, L.J., Butcher, S., Walsh, S., Wordsworth, P. and Sykes, B. (1995) Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II). Hum. Mol. Genet. 4, 1649-1651. MEDLINE Abstract

17 Toriello, H.V., Glover, T.W., Takahara, K., Byers, P.H., Miller, D.E., Higgins, J.V. and Greenspan, D.S. (1996) A translocation interrupts the COL5A1 gene in a patient with Ehlers-Danlos syndrome and hypomelanosis of Ito. Nature Genet. 13, 361-365. MEDLINE Abstract

18 Greenspan, D.S., Northrup, H., Au, K.S., McAllister, K.A., Francomano, C.A., Wenstrup, R.J., Marchuk, D.A. and Kwiatkowski, D.J. (1995) COL5A1: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos Syndrome type II. Genomics 25, 737-739. MEDLINE Abstract

19 Tiller, G.E., Polumbo, P.A. and Summar, M.L. (1994) Linkage mapping of the gene for type III collagen (COL3A1) to human chromosome 2q using a VNTR polymorphism. Genomics 20, 275-277. MEDLINE Abstract

20 Takahara, K., Sato, Y., Okazawa, K., Okamoto, N., Noda, A., Yaoi, Y. and Kato, I. (1991) Complete primary structure of human collagen [alpha]1(V) chain. J. Biol. Chem. 266, 13124-13129. MEDLINE Abstract

21 Greenspan, D.S., Cheng, W. and Hoffman, G.G. (1991) The pro-[alpha]1(V) collagen chain: complete primary structure, distribution of expression, and comparison with the pro-[alpha]1(XI) collagen chain. J. Biol. Chem. 266, 24727-24733. MEDLINE Abstract

22 Takahara, K., Hoffman, G.G. and Greenspan, D.S. (1995) Complete structural organization of the human [alpha]1(V) collagen gene (COL5A1): divergence from the conserved organization of other characterized fibrillar collagen genes. Genomics 29, 588-597. MEDLINE Abstract

23 Niyibizi, C., Fietzek, P. P., and van der Rest, M. (1984) Human placenta type V collagens. Evidence for the existence of an alpha 1(V) alpha 2(V) alpha 3(V) collagen molecule. J. Biol. Chem. 259, 14170-14174. MEDLINE Abstract

24 Fessler, L.I., Shigaki, N. and Fessler, J.H. (1985) Isolation of a new procollagen V chain from chick embryo tendon. J. Biol. Chem. 260, 13286-13293. MEDLINE Abstract

*To whom correspondence should be addressed

This page is maintained by OUP admin. Last updated Thu Oct 31 15:28:51 GMT 1996. Part of the OUP Journals World Wide Web service.Copyright Oxford University Press, 1996


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
 J. Biol. Chem.Home page
R. J. Wenstrup, J. B. Florer, J. M. Davidson, C. L. Phillips, B. J. Pfeiffer, D. W. Menezes, I. Chervoneva, and D. E. Birk
Murine Model of the Ehlers-Danlos Syndrome: col5a1 HAPLOINSUFFICIENCY DISRUPTS COLLAGEN FIBRIL ASSEMBLY AT MULTIPLE STAGES
J. Biol. Chem., May 5, 2006; 281(18): 12888 - 12895.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
F. Segev, E. Heon, W. G. Cole, R. J. Wenstrup, F. Young, A. R. Slomovic, D. S. Rootman, D. Whitaker-Menezes, I. Chervoneva, and D. E. Birk
Structural Abnormalities of the Cornea and Lid Resulting from Collagen V Mutations
Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 565 - 573.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Ge, N.-S. Seo, X. Liang, D. R. Hopkins, M. Hook, and D. S. Greenspan
Bone Morphogenetic Protein-1/Tolloid-related Metalloproteinases Process Osteoglycin and Enhance Its Ability to Regulate Collagen Fibrillogenesis
J. Biol. Chem., October 1, 2004; 279(40): 41626 - 41633.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Gopalakrishnan, W.-M. Wang, and D. S. Greenspan
Biosynthetic Processing of the Pro-{alpha}1(V)Pro-{alpha}2(V)Pro-{alpha}3(V) Procollagen Heterotrimer
J. Biol. Chem., July 16, 2004; 279(29): 30904 - 30912.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Unsold, W. N. Pappano, Y. Imamura, B. M. Steiglitz, and D. S. Greenspan
Biosynthetic Processing of the Pro-alpha 1(V)2Pro-alpha 2(V) Collagen Heterotrimer by Bone Morphogenetic Protein-1 and Furin-like Proprotein Convertases
J. Biol. Chem., February 8, 2002; 277(7): 5596 - 5602.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. Schalkwijk, M. C. Zweers, P. M. Steijlen, W. B. Dean, G. Taylor, I. M. van Vlijmen, B. van Haren, W. L. Miller, and J. Bristow
A Recessive Form of the Ehlers-Danlos Syndrome Caused by Tenascin-X Deficiency
N. Engl. J. Med., October 18, 2001; 345(16): 1167 - 1175.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
T. Brandt, E. Orberk, R. Weber, I. Werner, O. Busse, B. T. Muller, F. Wigger, A. Grau, C. Grond-Ginsbach, and I. Hausser
Pathogenesis of cervical artery dissections: Association with connective tissue abnormalities
Neurology, July 10, 2001; 57(1): 24 - 30.
[Abstract] [Full Text] [PDF]

Home page
 CLIN APPL THROMB HEMOSTHome page
R. Bick
State-of-the-Art Review: Vascular Thrombohemorrhagic Disorders: Hereditary and Acquired
Clinical and Applied Thrombosis/Hemostasis, July 1, 2001; 7(3): 178 - 194.
[PDF]

Home page
 J. Biol. Chem.Home page
Y. Imamura, I. C. Scott, and D. S. Greenspan
The Pro-alpha 3(V) Collagen Chain. COMPLETE PRIMARY STRUCTURE, EXPRESSION DOMAINS IN ADULT AND DEVELOPING TISSUES, AND COMPARISON TO THE STRUCTURES AND EXPRESSION DOMAINS OF THE OTHER TYPES V AND XI PROCOLLAGEN CHAINS
J. Biol. Chem., March 17, 2000; 275(12): 8749 - 8759.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
C. Grond-Ginsbach, R. Weber, J. Haas, E. Orberk, S. Kunz, O. Busse, I. Hausser, T. Brandt, and B. Wildemann
Mutations in the COL5A1 Coding Sequence Are Not Common in Patients With Spontaneous Cervical Artery Dissections
Stroke, September 1, 1999; 30 (9): e1887 - 1890.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Imamura, B. M. Steiglitz, and D. S. Greenspan
Bone Morphogenetic Protein-1 Processes the NH2-terminal Propeptide, and a Furin-like Proprotein Convertase Processes the COOH-terminal Propeptide of pro-alpha 1(V) Collagen
J. Biol. Chem., October 16, 1998; 273(42): 27511 - 27517.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Fichard, E. Tillet, F. Delacoux, R. Garrone, and F. Ruggiero
Human Recombinant alpha 1(V) Collagen Chain. HOMOTRIMERIC ASSEMBLY AND SUBSEQUENT PROCESSING
J. Biol. Chem., November 28, 1997; 272(48): 30083 - 30087.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Bouma, W. A. Cabral, W. G. Cole, and J. C. Marini
COL5A1 Exon 14 Splice Acceptor Mutation Causes a Functional Null Allele, Haploinsufficiency of alpha 1(V) and Abnormal Heterotypic Interstitial Fibrils in Ehlers-Danlos Syndrome II
J. Biol. Chem., April 13, 2001; 276(16): 13356 - 13364.
[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 (46)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Wenstrup, R. J.
Right arrow Articles by Cole, W. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wenstrup, R. J.
Right arrow Articles by Cole, W. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?