Identification of a Novel Mutation in the Myosin VIIA Motor Domain in a Family with Autosomal Dominant Hearing Loss (DFNA11)

• Published in: Audiology & neurotology Vol. 11; no. 3; pp. 157 - 164
• Main Authors: Di Leva, Francesca, D’Adamo, Pio, Cubellis, Maria Vittoria, D’Eustacchio, Angela, Errichiello, Monica, Saulino, Claudio, Auletta, Gennaro, Giannini, Pasquale, Donaudy, Francesca, Ciccodicola, Alfredo, Gasparini, Paolo, Franzè, Annamaria, Marciano, Elio
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2006; S. Karger AG
• Subjects: Amino Acid Sequence; Auditory Threshold; Base Sequence; Biological and medical sciences; Chromosome Disorders - genetics; Chromosome Mapping; Dyneins - chemistry; Dyneins - genetics; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Female; Genotype; Hearing Loss, Sensorineural - genetics; Humans; Male; Medical sciences; Models, Molecular; Molecular Sequence Data; Mutation, Missense - genetics; Myosin VIIa; Myosins - chemistry; Myosins - genetics; Non tumoral diseases; Original Paper; Otorhinolaryngology. Stomatology; Pedigree; Vestibular Diseases - complications; Vestibular Diseases - genetics; Dominant hearing loss; Missense mutation; Molecular modelling; Myosin VIIA; Motor head domain; Human; Family study; Auditory disorder; Identification; Hearing loss; Gene; Autosomal character; Myosin; ENT disease; Dominant character
• ISSN: 1420-3030; 1421-9700
• DOI: 10.1159/000091199

We ascertained a large Italian family with an autosomal dominant form of non-syndromic sensorineural hearing loss with vestibular involvement. A genome-wide scan found linkage to locus DFNA11. Sequencing of the MYO7A gene in the linked region identified a new missense mutation resulting in an Ala230Val change in the motor domain of the myosin VIIA. Myosin VIIA has already been implicated in several forms of deafness, but this is the third mutation causing a dominant form of deafness, located in the myosin VIIA motor domain in a region never involved in hearing loss until now. A modelled protein structure of myosin VII motor domain provides evidence for a significant functional effect of this missense mutation.