title: Identification of a novel nonsynonymous mutation of EYA1 disrupting splice site in a Korean patient with BOR syndrome.
abstract: The EYA1 gene is known as the causative gene of BOR (Branchio-oto-renal) syndrome which is a genetic disorder associated with branchial cleft cysts of fistulae, hearing loss, ear malformation, and renal anomalies. Although approximately 40% of patients with BOR syndrome have mutations in the EYA1 gene and over 130 disease-causing mutations in EYA1 have been reported in various populations, only a few mutations have been reported in Korean families. In this study, genetic analysis of the EYA1 gene was performed in a Korean patient diagnosed with BOR syndrome and his parents. A de novo novel missense mutation, c.418G>A, located at the end of exon 6, changed glycine to serine at amino acid position 140 (p.G140S) and was suspected to affect normal splicing. Our in vitro splicing assay demonstrated that this mutation causes exon 6 skipping leading to frameshift and truncation of the protein to result in the loss of eyaHR. To the best of our knowledge, this is the first report revealing that a missense mutation in the exon disturbs normal splicing as a result of a substitution of the last nucleotide of an exon in EYA1.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, 702-701, South Korea.
authors.forename: Hui Ram
authors.initials: HR
authors.lastname: Kim
authors.forename: Mee Hyun
authors.initials: MH
authors.lastname: Song
authors.forename: Min-A
authors.initials: MA
authors.lastname: Kim
authors.forename: Ye-Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
authors.forename: Jong Kyung
authors.initials: JK
authors.lastname: Sonn
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People; D001483:Base Sequence; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D022821:RNA Splice Sites
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D022821:RNA Splice Sites; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases