title: A novel TECTA mutation in a Dutch DFNA8/12 family confirms genotype-phenotype correlation.
abstract: A novel TECTA mutation, p.R1890C, was found in a Dutch family with nonsyndromic autosomal dominant sensorineural hearing impairment. In early life, presumably congenital, hearing impairment occurred in the midfrequency range, amounting to about 40 dB at 1 kHz. Speech recognition was good with all phoneme recognition scores exceeding 90%. An intact horizontal vestibuloocular reflex was found in four tested patients. The missense mutation is located in the zona pellucida (ZP) domain of alpha-tectorin. Mutations affecting the ZP domain of alpha-tectorin are significantly associated with midfrequency hearing impairment. Substitutions affecting other amino acid residues than cysteines show a significant association with hearing impairment without progression. Indeed, in the present family progression seemed to be absent. In addition, the presently identified mutation affecting the ZP domain resulted in a substantially lesser degree of hearing impairment than was previously reported for DFNA8/12 traits with mutations affecting the ZP domain of alpha-tectorin.
authors.affiliation: Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. r.plantinga@kno.umcn.nl
authors.forename: Rutger F
authors.initials: RF
authors.lastname: Plantinga
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: Henricus P M
authors.initials: HP
authors.lastname: Kunst
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: D000328:Adult; D001299:Audiometry; D004252:DNA Mutational Analysis; D004584:Electronystagmography; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins; D008040:Genetic Linkage; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D017434:Protein Structure, Tertiary; D013067:Speech Perception; D015044:Zona Pellucida
chemical_list: D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C491350:TECTA protein, human