Genetic etiology of hearing loss in Croatia in individuals negative for GJB2 variants
DOI:
https://doi.org/10.13112/pc.1055Keywords:
HEARING LOSS; EXOME SEQUENCING; MULTIPLEX POLYMERASE CHAIN REACTION; DNA COPY NUMBER VARIATIONSAbstract
Objective: To report on the spectrum and frequency of clinically relevant variants detected in 66 GJB2-negative patients with non-syndromic and 39 patients with syndromic hearing loss who underwent genetic testing at the Children's Hospital Zagreb between April 2019 and December 2024.
Methods: A multiplex ligation-dependent probe amplification method was used to analyze copy number variants in STRC and OTOA genes in 49 patients with non-syndromic hearing loss. Clinical exome sequencing was performed in patients negative for biallelic variants of GJB2, GJB6, OTOA, and STRC genes and patients with syndromic hearing loss, a total of 60.
Results: Biallelic variants in STRC and OTOA genes were not detected, probably due to the small study group and limitations of the applied methods. Clinical exome analysis in eight subjects with non-syndromic hearing loss revealed three autosomal dominant forms: DFNA8/12, DFNA11, and DFNA2A and three autosomal recessive forms: DFNB23/Usher syndrome type 1F, DFNB8/10, and DFNB3. 35 different variants in 21 genes were detected in 29 subjects with syndromic hearing loss, two of which in SIX1 and CHD7 genes were newly described. 19 different syndromes associated with hearing loss were found. 27.5 % (8/29) of positive patients with syndromic hearing loss had Usher syndrome type 2A with the variant c.11864G>A found in 62.5 % (5/8) of patients.
Conclusion: The high prevalence of the c.11864G>A variant in our population is likely due to a founder effect. Considering the heterogeneous etiology of hearing loss, its diagnosis is very complex and challenging, especially in complex syndromic forms where changes in different genes in the same patient can contribute to hearing impairment or its other clinical features.
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