CC BY-NC-ND 4.0 · Laryngorhinootologie 2019; 98(S 02): S310-S311
DOI: 10.1055/s-0039-1686362

Next generation sequencing of patients with hereditary neurosensory hearing loss to clarify the genetic cause of hearing impairment

V Dobriyanova
1   University Hospital 'Tsaritsa Joanna', Sofia, Bulgaria
D Popova
2   University Hospital, Sofia, Bulgaria
D Kachakova
3   Molecular Medicine Center, Department of Medical Chemistry and Biochemistry Medical University of Sofia, Sofia, Bulgaria
I Stancheva
2   University Hospital, Sofia, Bulgaria
S Varbanova
2   University Hospital, Sofia, Bulgaria
› Institutsangaben

The purpose of the study is a clinical and genetical diagnostics of families with family history of neurosensory hearing loss, defining clinical and genetical characteristics of the hearing damage by conducting a targetted new generation sequencing.

There were examined 193 patients with NSHL. In 31.05% (in 60 patients) using direct sequencing it was found a mutation in gene for connexin 26. Mutations for genes encoding Cx30, Cx31 and mitochondrial DNA mutations were not found in this group. We selected five patients and their families with family history of deafness in three ot more generations. Next generation sequencing was applied. Used panel included 212 genes associated with the development of deafness (both syndrome and non-syndrome).

A genetic cause for hearing loss was found out in two of them. When examining DF210 (family №5) the variant c.853G> A(p.Gly285Ser) in exon 6 of the KCNQ4 gene was found. The mutations in it are connected with the development of an autosomal dominant hearing loss. A genetic cause for a formation of NSHL is assumed and in patient DF139 (family №3), in whom was found a duplication of 51 basic pairs in OTOA gene, affecting exon 3 and partly intron 1 – 2 and intron 2 – 3. This is associated with a clinical phenotype in the autosomal recessive hearing loss. As regards to the patients DF60 (family №1) and DF182 (family №4), the found variants are insufficient to be associated with the particular clinical picture. There are not found pathological variants in DF84 (family №2), and AD inheritance is assumed.

Reasons for the inability to register genetic causes for the development of hearing loss in families №1, №2 and №4 are unclear. There have not been found all the genes causing a hearing loss up to the moment.


23. April 2019 (online)

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