Molecular study of 33 families with Fraser syndrome new data and mutation review

M. M. Van Haelst, M. Maiburg, G. Baujat, S. Jadeja, E. Monti, E. Bland, K. Pearce, R. C. Hennekam, P. J. Scambler, Lihadt Al-Gazali, Perez Aytes, Arianna Bonato, David Chitayat, Angus Dobbie, Dian Donnai, Frances Elmslie, Jose Ferreira, Christine Francannet, Brigitte Gilbert, John GrahamRaoul Hennekam, Sue Holder, Bronwyn Kerr, Saskia Maas, Andre Megarbane, Peter Meinecke, Serge Melancon, Alina Midro, John Nelson, Nicole Philip, Willie Reardon, Heiko Reutter, Heloise Santos, Peter Scambler, Christel Thauvin, Eva Todos, John Tolmie, Ton Van Essen, Andrew Wilkie, Louise Wilson

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


Fraser syndrome (FS) is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract. FS is considered to be the human equivalent of the murine blebbing mutants: in the mouse mutations at five loci cause a phenotype that is comparable to FS in humans, and thus far mutations in two syntenic human genes, FRAS1 and FREM2, have been identified to cause FS. Here we present the molecular analysis of 48 FS patients from 18 consanguineous and 15 nonconsanguineous families. Linkage analysis in consanguineous families indicated possible linkage to FRAS1 and FREM2 in 60% of the cases. Mutation analysis identified 11 new mutations in FRAS1 and one FREM2 mutation. Manifestations of these patients and previously reported cases with an FRAS1 mutation were compared to cases without detectable FRAS1 mutations to study genotype-phenotype correlations. Although our data suggest that patients with an FRAS1 mutation have more frequently skull ossification defects and low insertion of the umbilical cord, these differences are not statistically significant. Mutations were identified in only 43% of the cases suggesting that other genes syntenic to murine genes causing blebbing may be responsible for FS as well.

Original languageEnglish
Pages (from-to)2252-2257
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number17
Publication statusPublished - Sept 1 2008
Externally publishedYes


  • Cryptophtalmos
  • FRAS1/FREM2 mutations
  • Fraser syndrome
  • Genotype-phenotype correlation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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