Among 18 consanguineous families with Fraser syndrome, van Haelst et al. (2008) found 9 families with linkage to FRAS1, 3 families to FREM2, and 3 families to both genes. Six families did not link to either locus, indicating genetic heterogeneity. Among a larger group of 33 families, including the 18 consanguineous families, molecular analysis identified 11 novel mutations in the FRAS1 gene in 10 families and 1 mutation in the FREM2 gene (608945.0003) in 1 family. A literature review of genotype/phenotype correlations suggested that patients with FRAS1 mutations have more frequent skull ossification defects and a low insertion of the umbilical cord compared to patients without a FRAS1 mutation, but the findings were not statistically significant.
