Genotype-phenotype correlation in hereditary hearing loss

Mutations in 66 genes are known for autosomal recessive, in 36 genes for autosomal dominant and in 5 genes with x-linked non-syndromic types of hearing loss. Furthermore, there are known digenic mechanisms in hereditery hearing loss.

284 patients were selected for a retrospective analysis and we performed genetic diagnostics by panel diagnostic.

In more than 80% of the patients genetic mutations in hearing loss genes were detected, in 54% the diagnosis was secure or most likely to cause hereditary hearing loss. The most frequent genes were GJB2 (17%), MYO7A (8%), MYO15A (7%), TECTA (6%) and MYO6 (3%). The autosomal recessive forms of GJB2 (DFNB1A) and MYO7A (DFNB2) were associated with pre-lingual deafness. Patients with mutations in MYO15A (DFNB3) showed a variable beginning and progressive character of hearing loss. The clinical progress of the autosomal dominant forms in MYO7A (DFNA11), TECTA (DFNA8/DFNA12) and MYO6 (DFNA22) showed a later on-set of hearing impairment and manifestation of the deafness. CI-patients with GJB2-mutation showed the best hearing results (80% at 65dB). The speech perception of patients with mutations in MYO15A, TECTA und MYO6 was 70%, in patients with MYO7A-mutations 40%. Patients with mutated CACNAD1, MYO7A, LOXHD1, PTPRQ, CDH23, TFAP2A, COL9A3, TMPRSS3, GPR98 and TJP2 showed speech perception scores below 50%.

High throughput sequencing allows to diagnose known deafness genes. Genotype-phenotype-correlation allows predictions regarding the clinical course of hearing impairment. The treatment with a CI shows a good outcome for the most common genes GJB2, MYO15A, TECTA and MYO6.

Publication History

Publication Date:
18 April 2018 (online)