Bi-allelic inactivating variants in the COCH gene cause autosomal recessive prelingual hearing impairment
| Autor: | Nils Peeters, Sebastien P F JanssensdeVarebeke, Guy Van Camp, Kristof Deben, Ellen Elinck, Tony Cox, Wim Wuyts, Tom Crins, Josine Widdershoven, K. Ketelslagers |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nonsynonymous substitution Adult Male Hearing loss media_common.quotation_subject Nonsense Disease 030105 genetics & heredity Deafness Brief Communication Coch gene 03 medical and health sciences Loss of Function Mutation Reflex Genetics otorhinolaryngologic diseases Medicine Humans Sibling Allele Child Biology Genetics (clinical) Alleles media_common Vestibular system Extracellular Matrix Proteins business.industry Infant Pursuit Smooth Pedigree Chemistry 030104 developmental biology Codon Nonsense Female Human medicine sense organs Vestibule Labyrinth medicine.symptom business |
| Zdroj: | European journal of human genetics |
| ISSN: | 1476-5438 1018-4813 |
| Popis: | Pathogenic variant in COCH are a known cause of DFNA9 autosomal dominant progressive hearing loss and vestibular dysfunction with adult onset. Hitherto, only dominant nonsynonymous variants and in-frame deletions with a presumed dominant negative or gain-of-function effect have been described. Here, we describe two brothers with congenital prelingual deafness and a homozygous nonsense c.292C>T(p.Arg98*) COCH variant, suggesting a loss-of-function effect. Vestibular dysfunction starting in the first decade was observed in the older patient. The heterozygous parents and sibling have normal hearing and vestibular function, except for the mother, who shows vestibular hyporeflexia and abnormal smooth pursuit tests, most likely due to concomitant disease. This is the first report of autosomal recessive inheritance of cochlea-vestibular dysfunction caused by a pathogenic variant in the COCH gene. An earlier onset of hearing impairment and vestibular dysfunction compared to the dominant hearing loss causing COCH variants is observed. |
| Databáze: | OpenAIRE |
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