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