title: Expanding the mutation spectrum for Fraser syndrome: identification of a novel heterozygous deletion in FRAS1.
abstract: Fraser syndrome (FS) is a rare autosomal recessive inherited disorder characterized by cryptophthalmos, laryngeal defects and oral clefting, mental retardation, syndactyly, and urogenital defects. To date, 250 patients have been described in the literature. Mutations in the FRAS1 gene on chromosome 4 have been identified in patients with Fraser syndrome. So far, 26 mutations have been identified, most of them are truncating mutations. The mutational spectrum includes nucleotide substitutions, splicing defects, a large insertion, and small deletions/insertions. Moreover, single heterozygous missense mutations in FRAS1 seem to be responsible for non-syndromic unilateral renal agenesis. Here we report the first case of a family with two patients affected by Fraser syndrome due to a deletion of 64 kb (deletion 4q21.21) and an additional novel frameshift mutation in exon 66 of the FRAS1 gene. To date, large deletions of the FRAS1 gene have not yet been described. Large deletions seem to be a rare cause for Fraser syndrome, but should be considered in patients with a single heterozygous mutation.
authors.affiliation: Center for Human Genetics and Laboratory Medicine, Martinsried, Germany. julia.hoefele@medizinische-genetik.de
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefele
authors.forename: Christian
authors.initials: C
authors.lastname: Wilhelm
authors.forename: Monika
authors.initials: M
authors.lastname: Schiesser
authors.forename: Reinhold
authors.initials: R
authors.lastname: Mack
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinrich
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.forename: Saskia
authors.initials: S
authors.lastname: Biskup
authors.forename: Cornelia
authors.initials: C
authors.lastname: Daumer-Haas
authors.forename: Hanns-Georg
authors.initials: HG
authors.lastname: Klein
authors.forename: Imma
authors.initials: I
authors.lastname: Rost
mesh_terms: D037881:Aborted Fetus / Q000473:pathology; D000028:Abortion, Induced; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics / Q000502:physiology; D058497:Fraser Syndrome / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D010375:Pedigree; D011247:Pregnancy; D017384:Sequence Deletion / Q000502:physiology
chemical_list: D016326:Extracellular Matrix Proteins; C475145:FRAS1 protein, human