Skip Navigation

This Article
Right arrow Full Text 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 (164)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Cheadle, J. P.
Right arrow Articles by Clarke, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cheadle, J. P.
Right arrow Articles by Clarke, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2000, Vol. 9, No. 7 1119-1129
© 2000 Oxford University Press

Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location

Jeremy P. Cheadle, Harinder Gill+, Nick Fleming, Julie Maynard, Alison Kerr1, Helen Leonard2, Michael Krawczak, David N. Cooper, Sally Lynch3, Nick Thomas, Helen Hughes, Maj Hulten4, David Ravine, Julian R. Sampson and Angus Clarke§

Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK, 1Department of Psychological Medicine, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 OXH, UK, 2TVW Telethon Institute for Child Health Research, West Perth, WA 6872, Australia, 3Department of Human Genetics, University of Newcastle upon Tyne, 19/20 Claremont Place, Newcastle upon Tyne, NE2 4AA, UK and 4Department of Biological Sciences, University of Warwick, UK

Mutations in the methyl-CpG-binding protein gene MECP2 at Xq28 cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder characterized by a period of stagnation followed by regression in the development of young girls. Mutations were sought in MECP2 in 48 females with classical sporadic RTT, seven families with possible familial RTT and five sporadic females with features suggestive, but not diagnostic of RTT. Long distance PCR coupled with long-read direct sequencing was employed to sequence the entire MECP2 gene coding region in all cases. Mutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT. Twenty-one different mutations were identified (12 missense, four nonsense and five frame-shift mutations); 14 of these were novel. All missense mutations were located either in the methyl-CpG-binding domain or in the transcription repression domain. Nine recurrent mutations were characterized in a total of 33 unrelated cases (73% of all cases with MECP2 mutations). Significantly milder disease was noted in patients carrying missense mutations as compared with those with truncating mutations (P = 0.0023), and milder disease was associated with late as compared with early truncating mutations (P = 0.0190).

+ These authors contributed equally to this work

§ To whom correspondence should be addressed. Tel: +44 29 20744035; Fax: +44 29 20747603; Email: clarkeaj@cardiff.ac.uk


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
L. Rusconi, L. Salvatoni, L. Giudici, I. Bertani, C. Kilstrup-Nielsen, V. Broccoli, and N. Landsberger
CDKL5 Expression Is Modulated during Neuronal Development and Its Subcellular Distribution Is Tightly Regulated by the C-terminal Tail
J. Biol. Chem., October 31, 2008; 283(44): 30101 - 30111.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. Nectoux, N. Bahi-Buisson, I. Guellec, J. Coste, N. D. Roux, H. Rosas, M. Tardieu, J. Chelly, and T. Bienvenu
The p.Val66Met polymorphism in the BDNF gene protects against early seizures in Rett syndrome
Neurology, May 27, 2008; 70(22_Part_2): 2145 - 2151.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
Y. Zhang and B. A. Minassian
Will my Rett syndrome patient walk, talk, and use her hands?
Neurology, April 15, 2008; 70(16): 1302 - 1303.
[Full Text] [PDF]

Home page
 NeurologyHome page
J. L. Neul, P. Fang, J. Barrish, J. Lane, E. B. Caeg, E. O. Smith, H. Zoghbi, A. Percy, and D. G. Glaze
Specific mutations in Methyl-CpG-Binding Protein 2 confer different severity in Rett syndrome
Neurology, April 15, 2008; 70(16): 1313 - 1321.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. Bebbington, A. Anderson, D. Ravine, S. Fyfe, M. Pineda, N. de Klerk, B. Ben-Zeev, N. Yatawara, A. Percy, W. E. Kaufmann, et al.
Investigating genotype-phenotype relationships in Rett syndrome using an international data set
Neurology, March 11, 2008; 70(11): 868 - 875.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
P Huppke, E M Maier, A Warnke, C Brendel, F Laccone, and J Gartner
Very mild cases of Rett syndrome with skewed X inactivation
J. Med. Genet., October 1, 2006; 43(10): 814 - 816.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
C. L. Laurvick, M. E. Msall, S. Silburn, C. Bower, N. d. Klerk, and H. Leonard
Physical and Mental Health of Mothers Caring for a Child With Rett Syndrome
Pediatrics, October 1, 2006; 118(4): e1152 - e1164.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
H L Archer, S D Whatley, J C Evans, D Ravine, P Huppke, A Kerr, D Bunyan, B Kerr, E Sweeney, S J Davies, et al.
Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients
J. Med. Genet., May 1, 2006; 43(5): 451 - 456.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
H. Y. Zoghbi
MeCP2 Dysfunction in Humans and Mice
J Child Neurol, September 1, 2005; 20(9): 736 - 740.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
A. L. Ham, A. Kumar, R. Deeter, and N. C. Schanen
Does Genotype Predict Phenotype in Rett Syndrome?
J Child Neurol, September 1, 2005; 20(9): 768 - 778.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
H. Y. Zoghbi
MeCP2 Dysfunction in Humans and Mice
J Child Neurol, August 1, 2005; 20(8): 736 - 740.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
A. L. Ham, A. Kumar, R. Deeter, and N. C. Schanen
Does Genotype Predict Phenotype in Rett Syndrome?
J Child Neurol, August 1, 2005; 20(8): 768 - 778.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
H. Moore, H. Leonard, N. de Klerk, I. Robertson, S. Fyfe, J. Christodoulou, L. Weaving, M. Davis, S. Mulroy, and L. Colvin
Health Service Use in Rett Syndrome
J Child Neurol, January 1, 2005; 20(1): 42 - 50.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
Jong Hee Chae, Hee Hwang, Yong Seung Hwang, Hee Jung Cheong, and Ki Joong Kim
Influence of MECP2 Gene Mutation and X-Chromosome Inactivation on the Rett Syndrome Phenotype
J Child Neurol, July 1, 2004; 19(7): 503 - 508.
[Abstract] [PDF]

Home page
 NeuroscientistHome page
J. L. Neul and H. Y. Zoghbi
Rett Syndrome: A Prototypical Neurodevelopmental Disorder
Neuroscientist, April 1, 2004; 10(2): 118 - 128.
[Abstract] [PDF]

Home page
 Hum Mol GenetHome page
R. C. Samaco, R. P. Nagarajan, D. Braunschweig, and J. M. LaSalle
Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders
Hum. Mol. Genet., March 15, 2004; 13(6): 629 - 639.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. K. Inlow and L. L. Restifo
Molecular and Comparative Genetics of Mental Retardation
Genetics, February 1, 2004; 166(2): 835 - 881.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
L Colvin, H Leonard, N de Klerk, M Davis, L Weaving, S Williamson, and J Christodoulou
Refining the phenotype of common mutations in Rett syndrome
J. Med. Genet., January 1, 2004; 41(1): 25 - 30.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Kriaucionis and A. Bird
DNA methylation and Rett syndrome
Hum. Mol. Genet., October 15, 2003; 12(90002): R221 - 227.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
S. Naidu, G. Bibat, L. Kratz, R. I. Kelley, J. Pevsner, E. Hoffman, C. Cuffari, C. Rohde, M. E. Blue, and M. V. Johnston
Clinical Variability in Rett Syndrome
J Child Neurol, October 1, 2003; 18(10): 662 - 668.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
J. Christodoulou and L. S. Weaving
MECP2 and Beyond: Phenotype--Genotype Correlations in Rett Syndrome
J Child Neurol, October 1, 2003; 18(10): 669 - 674.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
S. Fyfe, A. Cream, N. de Klerk, J. Christodoulou, and H. Leonard
InterRett and RettBASE: International Rett Syndrome Association Databases for Rett Syndrome
J Child Neurol, October 1, 2003; 18(10): 709 - 713.
[Abstract] [PDF]

Home page
 J. Med. Genet.Home page
S Kudo, Y Nomura, M Segawa, N Fujita, M Nakao, C Schanen, and M Tamura
Heterogeneity in residual function of MeCP2 carrying missense mutations in the methyl CpG binding domain
J. Med. Genet., July 1, 2003; 40(7): 487 - 493.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
H Gill, J P Cheadle, J Maynard, N Fleming, S Whatley, T Cranston, E M Thompson, H Leonard, M Davis, J Christodoulou, et al.
Mutation analysis in the MECP2 gene and genetic counselling for Rett syndrome
J. Med. Genet., May 1, 2003; 40(5): 380 - 384.
[Full Text] [PDF]

Home page
 J. Med. Genet.Home page
H Leonard, L Colvin, J Christodoulou, T Schiavello, S Williamson, M Davis, D Ravine, S Fyfe, N de Klerk, T Matsuishi, et al.
Patients with the R133C mutation: is their phenotype different from patients with Rett syndrome with other mutations?
J. Med. Genet., May 1, 2003; 40(5): e52 - 52.
[Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. F. Fraga, E. Ballestar, G. Montoya, P. Taysavang, P. A. Wade, and M. Esteller
The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties
Nucleic Acids Res., March 15, 2003; 31(6): 1765 - 1774.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
H Turner, F MacDonald, S Warburton, F Latif, and T Webb
Developmental delay and the methyl binding genes
J. Med. Genet., February 1, 2003; 40(2): e13 - 13.
[Full Text] [PDF]

Home page
 J Child NeurolHome page
G. M. Liebhaber, E. Riemann, and F. A. Matthias Baumeister
Ketogenic Diet in Rett Syndrome
J Child Neurol, January 1, 2003; 18(1): 74 - 75.
[Abstract] [PDF]

Home page
 J. Med. Genet.Home page
K Ravn, J B Nielsen, P Uldall, F J Hansen, and M Schwartz
No correlation between phenotype and genotype in boys with a truncating MECP2 mutation
J. Med. Genet., January 1, 2003; 40(1): e5 - 5.
[Full Text] [PDF]

Home page
 Arch. Dis. Child.Home page
L Colvin, S Fyfe, S Leonard, T Schiavello, C Ellaway, N de Klerk, J Christodoulou, M Msall, and H Leonard
Describing the phenotype in Rett syndrome using a population database
Arch. Dis. Child., January 1, 2003; 88(1): 38 - 43.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
F Laccone, B Zoll, P Huppke, F Hanefeld, W Pepinski, and R Trappe
MECP2 gene nucleotide changes and their pathogenicity in males: proceed with caution
J. Med. Genet., August 1, 2002; 39(8): 586 - 588.
[Full Text] [PDF]

Home page
 J Child NeurolHome page
B. Ben Zeev, Y. Yaron, N. C. Schanen, H. Wolf, N. Brandt, N. Ginot, R. Shomrat, and A. Orr-Urtreger
Rett Syndrome: Clinical Manifestations in Males With MECP2 Mutations
J Child Neurol, January 1, 2002; 17(1): 20 - 24.
[Abstract] [PDF]

Home page
 J Child NeurolHome page
Jong Hee Chae, Yong Seung Hwang, and Ki Joong Kim
Mutation Analysis of MECP2 and Clinical Characterization in Korean Patients With Rett Syndrome
J Child Neurol, January 1, 2002; 17(1): 33 - 36.
[Abstract] [PDF]

Home page
 J. Med. Genet.Home page
V. Bourdon, C. Philippe, T. Bienvenu, B. Koenig, M. Tardieu, J. Chelly, and P. Jonveaux
Evidence of somatic mosaicism for a MECP2 mutation in females with Rett syndrome: diagnostic implications
J. Med. Genet., December 1, 2001; 38(12): 867 - 871.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. M. LaSalle, J. Goldstine, D. Balmer, and C. M. Greco
Quantitative localization of heterogeneous methyl-CpG-binding protein 2 (MeCP2) expression phenotypes in normal and Rett syndrome brain by laser scanning cytometry
Hum. Mol. Genet., August 1, 2001; 10(17): 1729 - 1740.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. Hoffbuhr, J. M. Devaney, B. LaFleur, N. Sirianni, C. Scacheri, J. Giron, J. Schuette, J. Innis, M. Marino, M. Philippart, et al.
MeCP2 mutations in children with and without the phenotype of Rett syndrome
Neurology, June 12, 2001; 56(11): 1486 - 1495.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
H. Leonard, J. Silberstein, R. Falk, I. Houwink-Manville, C. Ellaway, L. S. Raffaele, I. Witt Engerstrom, and C. Schanen
Occurrence of Rett Syndrome in Boys
J Child Neurol, May 1, 2001; 16(5): 333 - 338.
[Abstract] [PDF]

Home page
 Hum Mol GenetHome page
P. Couvert, T. Bienvenu, C. Aquaviva, K. Poirier, C. Moraine, C. Gendrot, A. Verloes, C. Andres, A. C. Le Fevre, I. Souville, et al.
MECP2 is highly mutated in X-linked mental retardation
Hum. Mol. Genet., April 1, 2001; 10(9): 941 - 946.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
T. Webb and F. Latif
Rett syndrome and the MECP2 gene
J. Med. Genet., April 1, 2001; 38(4): 217 - 223.
[Full Text]

Home page
 NeurologyHome page
M. Auranen, R. Vanhala, M. Vosman, M. Levander, T. Varilo, M. Hietala, R. Riikonen, L. Peltonen, and I. Jarvela
MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like features
Neurology, March 13, 2001; 56(5): 611 - 617.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. M. Yusufzai and A. P. Wolffe
Functional consequences of Rett syndrome mutations on human MeCP2
Nucleic Acids Res., November 1, 2000; 28(21): 4172 - 4179.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
L. Villard, A. Kpebe, C. Cardoso, J. Chelly, M. Tardieu, and M. Fontes
Two affected boys in a Rett syndrome family: Clinical and molecular findings
Neurology, October 24, 2000; 55(8): 1188 - 1193.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Dragich, I. Houwink-Manville, and C. Schanen
Rett syndrome: a surprising result of mutation in MECP2
Hum. Mol. Genet., October 1, 2000; 9(16): 2365 - 2375.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Huppke, F. Laccone, N. Kramer, W. Engel, and F. Hanefeld
Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients
Hum. Mol. Genet., May 22, 2000; 9(9): 1369 - 1375.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Free, R. I. D. Wakefield, B. O. Smith, D. T. F. Dryden, P. N. Barlow, and A. P. Bird
DNA Recognition by the Methyl-CpG Binding Domain of MeCP2
J. Biol. Chem., January 26, 2001; 276(5): 3353 - 3360.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.