Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families

Wendy Chang, Thomas L. Winder, Charles A. LeDuc, Lynn L. Simpson, William S. Millar, Jeffrey Dungan, Norman Ginsberg, Stacey Plaga, Steven A. Moore, Wendy K. Chung

Research output: Contribution to journalArticle

Abstract

Objective: Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (α-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. Method: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)560-569
Number of pages10
JournalPrenatal Diagnosis
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • Genetic screening
  • Muscle-eye-brain disease

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Genetics(clinical)

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    Chang, W., Winder, T. L., LeDuc, C. A., Simpson, L. L., Millar, W. S., Dungan, J., Ginsberg, N., Plaga, S., Moore, S. A., & Chung, W. K. (2009). Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families. Prenatal Diagnosis, 29(6), 560-569. https://doi.org/10.1002/pd.2238