Ethnically diverse causes of walker-warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the middle east

M. Chiara Manzini, Danielle Gleason, Bernard S. Chang, R. Sean Hill, Brenda J. Barry, Jennifer N. Partlow, Annapurna Poduri, Sophie Currier, Patricia Galvin-Parton, Lawrence R. Shapiro, Karen Schmidt, Jessica G. Davis, Lina Basel-Vanagaite, Mohamed Z. Seidahmed, Mustafa A.M. Salih, William B. Dobyns, Christopher A. Walsh

Research output: Contribution to journalArticle

47 Scopus citations

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 α-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.

Original languageEnglish (US)
Pages (from-to)E231-E241
JournalHuman mutation
Volume29
Issue number11
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Keywords

  • Alpha-dystroglycan
  • Congenital muscular dystrophy
  • POMT1, POMT2, FCMD, FKRP
  • Walker-warburg syndrome

Fingerprint Dive into the research topics of 'Ethnically diverse causes of walker-warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the middle east'. Together they form a unique fingerprint.

  • Cite this

    Manzini, M. C., Gleason, D., Chang, B. S., Hill, R. S., Barry, B. J., Partlow, J. N., Poduri, A., Currier, S., Galvin-Parton, P., Shapiro, L. R., Schmidt, K., Davis, J. G., Basel-Vanagaite, L., Seidahmed, M. Z., Salih, M. A. M., Dobyns, W. B., & Walsh, C. A. (2008). Ethnically diverse causes of walker-warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the middle east. Human mutation, 29(11), E231-E241. https://doi.org/10.1002/humu.20844