title: A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus.
abstract: Lymphedema-distichiasis (LD) syndrome is a clinically variable autosomal dominant disorder. The disorder is caused by mutations in the forkhead transcription factor FOXC2 gene on chromosome band 16q24.3. Here, we report the sequence of the FOXC2 gene in a German-Irish family with LD in six affected relatives over three generations and identify a single adenine base pair insertion at nt 1006--1007. This insertion creates a frameshift mutation that predicts a premature stop at codon 462. In addition to LD, four of the affected family members have renal disease and three have diabetes mellitus (DM), not usually seen in the LD syndrome. Polymorphisms of FOXC2 in diabetics have been studied in different populations. Our sequence analysis of the 5' untranslated region (UTR) C-512T shows the homozygous T allele in all family members tested. The sequencing data in this family suggests the possibility of a novel phenotype-haplotype. This novel phenotype, LD/renal disease/type 2 diabetes, might be the result of a combination of the nt 1006--1007 insA and the upstream UTR homozygous T polymorphism.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMDNJ, Newark, New Jersey 07103, USA.
authors.forename: Cagri
authors.initials: C
authors.lastname: Yildirim-Toruner
authors.forename: Kavitha
authors.initials: K
authors.lastname: Subramanian
authors.forename: Lamya
authors.initials: L
authors.lastname: El Manjra
authors.forename: Emily
authors.initials: E
authors.lastname: Chen
authors.forename: Stanley
authors.initials: S
authors.lastname: Goldstein
authors.forename: Emilia
authors.initials: E
authors.lastname: Vitale
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D004247:DNA; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D051858:Forkhead Transcription Factors; D016368:Frameshift Mutation; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008209:Lymphedema / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein; D004247:DNA