Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East.
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.
Manzini
M Chiara
MC
Division of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Gleason
Danielle
D
Chang
Bernard S
BS
Hill
R Sean
RS
Barry
Brenda J
BJ
Partlow
Jennifer N
JN
Poduri
Annapurna
A
Currier
Sophie
S
Galvin-Parton
Patricia
P
Shapiro
Lawrence R
LR
Schmidt
Karen
K
Davis
Jessica G
JG
Basel-Vanagaite
Lina
L
Seidahmed
Mohamed Z
MZ
Salih
Mustafa A M
MA
Dobyns
William B
WB
Walsh
Christopher A
CA