1. Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East.
- Author
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Manzini MC, Gleason D, Chang BS, Hill RS, Barry BJ, Partlow JN, Poduri A, Currier S, Galvin-Parton P, Shapiro LR, Schmidt K, Davis JG, Basel-Vanagaite L, Seidahmed MZ, Salih MA, Dobyns WB, and Walsh CA
- Subjects
- Abnormalities, Multiple ethnology, Child, Cobblestone Lissencephaly ethnology, Cobblestone Lissencephaly genetics, DNA Mutational Analysis, Eye Abnormalities ethnology, Eye Abnormalities genetics, Female, Genome, Human, Genotype, Humans, Male, Middle East, Muscular Dystrophies ethnology, Muscular Dystrophies genetics, Pedigree, Phenotype, Syndrome, Abnormalities, Multiple genetics, Membrane Proteins genetics, Mutation
- Abstract
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 á-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., ((c) 2008 Wiley-Liss, Inc.)
- Published
- 2008
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