Document Detail

The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation.
MedLine Citation:
PMID:  16575835     Owner:  NLM     Status:  MEDLINE    
The importance of O-glycosylation of alpha-dystroglycan (alpha-DG) is evident from the identification of POMT1 mutations in Walker-Warburg syndrome (WWS). Approximately one-fifth of the WWS patients show mutations in POMT1, which result in complete loss of protein mannosyltransferase activity. WWS patients are characterized by congenital muscular dystrophy (CMD) with severe brain and eye abnormalities. This suggests a crucial role for alpha-DG during development of these organs and tissues. Here we report new POMT1 mutations and polymorphisms in WWS patients. In addition, we report different compound heterozygous POMT1 mutations in four unrelated families that result in a less severe phenotype than WWS, characterized by CMD with calf hypertrophy, microcephaly, and mental retardation. Compared to WWS patients, these patients have milder structural brain abnormalities, and eye abnormalities were absent, except for myopia in some cases. In these patients we postulate that one or both transcripts for POMT1 confer residual protein O-mannosyltransferase activity. Our data suggest the existence of a disease spectrum of CMD including brain and eye abnormalities resulting from POMT1 mutations.
Jeroen van Reeuwijk; Svetlana Maugenre; Christa van den Elzen; Aad Verrips; Enrico Bertini; Francesco Muntoni; Luciano Merlini; Hans Scheffer; Han G Brunner; Pascale Guicheney; Hans van Bokhoven
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human mutation     Volume:  27     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-25     Completed Date:  2006-06-16     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-9     Citation Subset:  IM    
Copyright Information:
(c) 2006 Wiley-Liss, Inc.
Data Bank Information
Bank Name/Acc. No.:
OMIM/236670;  607423;  609308
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MeSH Terms
Brain / abnormalities,  pathology
Child, Preschool
Chromosome Mapping
DNA Mutational Analysis
Dystroglycans / genetics,  metabolism
Eye Abnormalities / genetics
Intellectual Disability / diagnosis,  genetics*,  pathology
Mannosyltransferases / genetics*,  metabolism
Microcephaly / diagnosis,  genetics*,  pathology
Microsatellite Repeats
Muscular Dystrophies / diagnosis,  genetics*,  pathology
Polymorphism, Genetic
Grant Support
G0502130//Medical Research Council
Reg. No./Substance:
0/DAG1 protein, human; 146888-27-9/Dystroglycans; EC 2.4.1.-/Mannosyltransferases; EC O-mannosyltransferase

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