TY - JOUR
T1 - Ethnically diverse causes of walker-warburg syndrome (WWS)
T2 - FCMD mutations are a more common cause of WWS outside of the middle east
AU - Manzini, M. Chiara
AU - Gleason, Danielle
AU - Chang, Bernard S.
AU - Hill, R. Sean
AU - Barry, Brenda J.
AU - Partlow, Jennifer N.
AU - Poduri, Annapurna
AU - Currier, Sophie
AU - Galvin-Parton, Patricia
AU - Shapiro, Lawrence R.
AU - Schmidt, Karen
AU - Davis, Jessica G.
AU - Basel-Vanagaite, Lina
AU - Seidahmed, Mohamed Z.
AU - Salih, Mustafa A.M.
AU - Dobyns, William B.
AU - Walsh, Christopher A.
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
KW - Alpha-dystroglycan
KW - Congenital muscular dystrophy
KW - POMT1, POMT2, FCMD, FKRP
KW - Walker-warburg syndrome
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U2 - 10.1002/humu.20844
DO - 10.1002/humu.20844
M3 - Article
C2 - 18752264
AN - SCOPUS:55549126862
SN - 1059-7794
VL - 29
SP - E231-E241
JO - Human mutation
JF - Human mutation
IS - 11
ER -