Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East
✍ Scribed by M. Chiara Manzini; Danielle Gleason; Bernard S. Chang; R. Sean Hill; Brenda J. Barry; Jennifer N. Partlow; Annapurna Poduri; Sophie Currier; Patricia Galvin-Parton; Lawrence R. Shapiro; Karen Schmidt; Jessica G. Davis; Lina Basel-Vanagaite; Mohamed Z. Seidahmed; Mustafa A. M. Salih; William B. Dobyns; Christopher A. Walsh
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 582 KB
- Volume
- 29
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
Walker-Warburg syndrome (WWS) is a genetically heterogeneous autosomal recessive disease characterized by congenital muscular dystrophy, cobblestone lissencephaly, and ocular malformations. Mutations in six genes involved in the glycosylation of α-dystroglycan (POMT1, POMT2, POMGNT1, FCMD, FKRP and LARGE) have been identified in WWS patients, but account for only a portion of WWS cases. To better understand the genetics of WWS and establish the frequency and distribution of mutations across WWS genes, we genotyped all known loci in a cohort of 43 WWS patients of varying geographical and ethnic origin. Surprisingly, we reached a molecular diagnosis for 40% of our patients and found mutations in POMT1, POMT2, FCMD and FKRP, many of which were novel alleles, but no mutations in POMGNT1 or LARGE. Notably, the FCMD gene was a more common cause of WWS than previously expected in the European/American subset of our cohort, including all Ashkenazi Jewish cases, who carried the same founder mutation.