Re-Classification of the Causes of Hereditary Hearing Impairment based on past data

Causal mutations for genetic hearing loss were described in 128 genes. A retrospective analysis of genetic findings based on gene panels of genes known for hearing loss was performed on 354 patients. In the period 2011-2018, 84% of the patients were diagnosed with a genetic variant, in 53% of the patients a genetic cause for hearing loss was likely or very likely, with 58 genes involved and a further 22 genes not involved. Based on known knowledge over time, the genes GJB2 (17.0%), MYO15A (7.9%), MYO7A (6.9%), TECTA (4.8%), WSF1 and TMPRSS3 (3.2%), COL11A1, COL11A2, and MYO6 (2.7%) were classified as the most frequent causes of hearing impairment.

In addition, the primary results showed pathogenic variants in the genes MYO1A (8 cases, 2.1%) and GJB6 (2 cases) as the cause of genetic hearing loss. After re-classification based on the current literature, the classifications as hearing loss associated genes for MYO1A and GJB6 cannot be maintained. This means that in these patients there is another mutation in a presumably unknown gene that causes hearing loss. These patients may require re-analysis with exom or genome sequencing to obtain a genetic diagnosis. The re-analysis also shows with frequently affected genes such as MYO15A that some of the variants assumed to be pathogenic can also no longer be classified as pathogenic.

In summary, data that were examined before consensus for variant interpretation was established should be re-analysed at certain time intervals in order to take current classifications into account.

Poster-PDF A-1839.PDF

Publication History

Article published online:
10 June 2020