title: Alpha-tectorin involvement in hearing disabilities: one gene--two phenotypes.
abstract: The human alpha-tectorin (TECTA) gene has recently been cloned and proposed to be involved in autosomal dominant non-syndromic hearing impairment (NSHI) in two families linked to the DFNA12 locus. We have studied a Swedish pedigree with autosomal dominant NSHI with possible digenic inheritance of the disease, involving locus DFNA12 in chromosome 11 and locus DFNA2 in chromosome 1. Mutation analysis of the TECTA gene in this family has identified eight nucleotide substitutions indicating that TECTA is highly polymorphic. One of the changes results in a cysteine to serine (C 1057 S) mutation, in the zonadhesin domain of TECTA; this segregates with the disease haplotype on chromosome 11 and is not present in a control population. The mutation results in the replacement of a cysteine in one of the repeats of the zonadhesin/Von Willebrand domain of the protein and might cause a change in the crosslinking of the polypeptide. These findings add support to the involvement of TECTA in hearing disabilities. However, the three families carrying different TECTA mutations also show phenotypic differences: the hearing loss ranges from prelingual to progressive with late onset. The explanation for the different phenotypes and some clues regarding the functions of TECTA may lie in the localization of the mutations in the different modules of the protein. Another possibility is that the phenotype in the Swedish family is the result of two defective genes.
authors.affiliation: Unit of Medical Genetics, Department of Genetics and Pathology, Uppsala University, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Balciuniene
authors.forename: N
authors.initials: N
authors.lastname: Dahl
authors.forename: P
authors.initials: P
authors.lastname: Jalonen
authors.forename: K
authors.initials: K
authors.lastname: Verhoeven
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: E
authors.initials: E
authors.lastname: Borg
authors.forename: U
authors.initials: U
authors.lastname: Pettersson
authors.forename: E E
authors.initials: EE
authors.lastname: Jazin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D058851:GPI-Linked Proteins; D005787:Gene Frequency; D006239:Haplotypes; D006311:Hearing Disorders / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid; D013548:Sweden
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C491350:TECTA protein, human; D004247:DNA