A cysteine substitution in the zona pellucida domain of α-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family
- Miguel Angel Moreno-Pelayoa,
- Ignacio del Castilloa,
- Manuela Villamara,
- Lourdes Romeroa,
- Francisco Javier Hernández-Calvínb,
- Carlos Herraizb,
- Rafael Barberác,
- Cristina Navasc,
- Felipe Morenoa
- aUnidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar Km 9, 28034 Madrid, Spain, bServicio de ORL, Centro Nacional de Especialidades Quirúrgicas, Pabellón 8, Ciudad Universitaria, Madrid, Spain, cServicio de ORL, Hospital Ramón y Cajal, Madrid, Spain
- Dr Moreno,
So far, 37 different loci for autosomal dominant, sensorineural, non-syndromic hearing loss (ADSNSHL), have been mapped and 11 genes have been cloned.1 Among them, theTECTA gene, mapped to chromosome 11q22-24 (locus DFNA8/A12), encodes α-tectorin,2 a non-collagenous component of the cochlear tectorial membrane. This membrane is an extracellular matrix that covers the apical surface of the sensory epithelium in the cochlea and plays an important role in transmitting the mechanical energy of sound to the mechanosensitive stereociliary bundles of the hair cells, where the sound is transduced into neural potentials. In previous studies, five different missense mutations resulting in ADSNSHL have been described in the TECTA gene in fourDFNA8/A12 families, affecting different domains of the protein and showing different phenotypes (table 1): a prelingual, non-progressive hearing loss affecting mid frequencies or a postlingual, progressive, high frequency hearing impairment.
In this study, we report a Spanish family with a novel phenotype of postlingual, progressive, mid frequency hearing loss resulting from a new mutation in the TECTA gene.
Materials and methods
The family consists of 47 members including nine affected subjects with ADSNSHL (fig 1A). Appropriate informed consent was obtained from all those studied. Clinical examination was performed and blood samples were obtained from 33 family members. Environmental factors were eliminated as the cause of deafness in all affected family members. Features suggestive of syndromic anomalies were not present. Otoscopic examination and use of the tuning fork test ruled out conductive hearing loss. Pure tone audiometry was performed to test for air conduction (frequencies of 125-8000 Hz) and bone conduction (frequencies of 250-8000 Hz). Affected subjects showed bilateral sensorineural hearing impairment. In the beginning, the hearing loss in this family is mild, mainly affecting mid frequencies (500, 1000, and …