Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families.
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.
Chang
Wendy
W
Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA. wkc15@columbia.edu
Winder
Thomas L
TL
LeDuc
Charles A
CA
Simpson
Lynn L
LL
Millar
William S
WS
Dungan
Jeffrey
J
Ginsberg
Norman
N
Plaga
Stacey
S
Moore
Steven A
SA
Chung
Wendy K
WK
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
C113587:FKTN protein, human; D008565:Membrane Proteins