title: Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families.
abstract: OBJECTIVE
  Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan (alpha-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS.
  
  
  METHODS
  We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis.
  
  
  RESULTS
  We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults.
  
  
  CONCLUSIONS
  These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population.
authors.affiliation: Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA. wkc15@columbia.edu
authors.forename: Wendy
authors.initials: W
authors.lastname: Chang
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Winder
authors.forename: Charles A
authors.initials: CA
authors.lastname: LeDuc
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Simpson
authors.forename: William S
authors.initials: WS
authors.lastname: Millar
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Dungan
authors.forename: Norman
authors.initials: N
authors.lastname: Ginsberg
authors.forename: Stacey
authors.initials: S
authors.lastname: Plaga
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities*; D002675:Child, Preschool; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007585:Jews / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000000981:diagnostic imaging / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D013577:Syndrome; D016216:Ultrasonography, Prenatal
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins