title: Mutation analysis of the FRAS1 gene demonstrates new mutations in a propositus with Fraser syndrome.
abstract: Fraser syndrome (OMIM 219000) is a rare, autosomal recessive condition with classical features of cryptophthalmos, syndactyly, ambiguous genitalia, laryngeal, and genitourinary malformations, oral clefting and mental retardation. Mutations causing loss of function of the FRAS1 gene have been demonstrated in five patients with Fraser syndrome. However, no phenotype-genotype correlation was established and there was evidence for genetic heterogeneity. Fraser syndrome is rare and the FRAS1 gene has 75 exons, complicating mutation screening in affected patients. We have screened two patients who fulfilled the diagnostic criteria for Fraser syndrome and three patients with related phenotypes (two patients with Manitoba oculotrichoanal syndrome and one patient with unilateral cryptophthalmos and labial fusion) for mutations in FRAS1 to increase the molecular genetic data in patients with Fraser syndrome and related conditions. We report two new mutations in a patient with Fraser syndrome, a frameshift mutation and a deletion of two amino acids that we consider pathogenic as both alter the NG2-like domain of the protein. Although we are still unable to clarify a phenotype-genotype relationship in Fraser syndrome, our data add to the list of mutations associated with this syndrome.
authors.affiliation: Department of Pediatrics, Division of Clinical Genetics, University of California, San Francisco, California 94143-0748, USA. slatovia@peds.ucsf.edu
authors.forename: A
authors.initials: A
authors.lastname: Slavotinek
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: E H
authors.initials: EH
authors.lastname: Sherr
authors.forename: A E
authors.initials: AE
authors.lastname: Chudley
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005143:Eyelids / Q000002:abnormalities*; D019066:Facies; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D009154:Mutation; D017384:Sequence Deletion; D013576:Syndactyly / Q000235:genetics*; D013577:Syndrome
chemical_list: D016326:Extracellular Matrix Proteins; C475145:FRAS1 protein, human