title: Novel TECTA mutations identified in stable sensorineural hearing loss and their clinical implications.
abstract: TECTA is a causative gene of autosomal dominant (DFNA8/A12) and autosomal recessive (DFNB 21) nonsyndromic sensorineural hearing loss (NSHL). Mutations in TECTA account for 4% of all autosomal dominant NSHL cases in some populations and are thus thought to be one of the major causes of autosomal dominant NSHL. A genotype-phenotype correlation for autosomal dominant mutations in the TECTA gene has been proposed. Two families (SB146 and SB149), which segregated moderate NSHL in an autosomal dominant fashion, were included in this study. We performed targeted resequencing of 134 known deafness genes (TRS-134) and bioinformatics analyses to find causative mutations for NSHL in these 2 families. Through TRS-134, we detected 2 novel mutations, i.e. c.3995G>T (p.C1332F) and c.5618C>T (p.T1873I), in the TECTA gene. These mutations cosegregated with NSHL in the studied families and were not detected in normal controls. The mutations c.3995G>T and c.5618C>T reside in the von Willebrand factor type D3-D4 (vWFD3-D4) interdomain of the zonadhesin (ZA) domain and the zona pellucida (ZP) domain, respectively. p.C1332F is the first mutation detected in the vWFD3-D4 interdomain of the ZA domain. The mutations p.C1332F and p.T1873I were associated with stable high-frequency and mid-frequency hearing loss, respectively. Notably, the cysteine residue mutated to phenylalanine in SB146 was not related to progression of sensorineural hearing loss, which argues against the previous hypothesis. Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. This clinical feature makes subjects with the missense mutation in the vWFD3-D4 interdomain of TECTA potentially good candidates for middle ear implantation.
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Kim
authors.forename: Mun Young
authors.initials: MY
authors.lastname: Chang
authors.forename: Ja-Won
authors.initials: JW
authors.lastname: Koo
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Oh
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005799:Genes, Dominant; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; C491350:TECTA protein, human