title: A novel TECTA mutation confirms the recognizable phenotype among autosomal recessive hearing impairment families.
abstract: Mutations in the TECTA gene result in sensorineural non-syndromic hearing impairment. TECTA-related deafness can be inherited autosomal dominantly (designated as DFNA8/12) or autosomal recessively (as DFNB21). The alpha-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Six mutations in the TECTA gene have already been reported in families segregating autosomal recessive non-syndromic hearing impairment. In this study, seventy-five Iranian families segregating autosomal recessive non-syndromic hearing impairment were analyzed for homozygosity at the DFNB21 locus by genotyping two short tandem repeat markers closely linked to the TECTA gene. Allelic segregation consistent with possible linkage to the DFNB21 locus was found in 1/75 families studied. By sequencing all 23 coding exons of TECTA, a 16bp deletion (c.6203-6218del16) in exon 21, leading to a frameshift, segregating with the hearing loss was found. All 3 affected individuals of this family have moderate-to-severe hearing loss across all frequencies, which is more pronounced in the mid frequencies. This new mutation, as well as the six previously reported mutations in the TECTA gene, is inactivating. All of these mutations lead to an easily recognized audiometric profile of moderate to severe hearing impairment as presented by the family in this study too. The TECTA autosomal recessive non-syndromic deafness phenotype differs from the typical profound deafness phenotype that is seen in most families segregating autosomal recessive non-syndromic deafness. On the basis of the recognizable phenotype, we recommend mutation screening of TECTA in families with this hearing phenotype.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Alasti
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Sanati
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Behrouzifard
authors.forename: Abdorrahim
authors.initials: A
authors.lastname: Sadeghi
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D003241:Consanguinity; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D058851:GPI-Linked Proteins; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007492:Iran; D008562:Membrane Glycoproteins / Q000235:genetics*; D010641:Phenotype; D020539:Sequence Analysis, Protein; D020080:Tandem Repeat Sequences
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; C491350:TECTA protein, human