• Ivona Sansović, Ana-Maria Meašić, Ljubica Odak, and Mijana Kero.
• Ivona Sansović, Children's Hospital Zagreb, Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Klaićeva 16, 10 000 Zagreb, Croatia, ivonas3010@gmail.com.
• Croat. Med. J. 2023 Oct 31; 64 (5): 329333329-333.

AbstractMissense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndromic hearing loss (ADNSHL) and account for a considerable number of ADNSHL cases. According to genotype-phenotype correlation studies, missense variants in the zona pellucida (ZP) domain of α-tectorin predominantly cause mid-frequency HL. Here, we report on clinical exome sequencing results in a large family with early-onset, sensorineural, moderate-to-severe mid-frequency HL. We identified one heterozygous c.6183G>T variant near the ZP domain of TECTA segregating in five family members. This variant was previously reported as a variant of uncertain significance in a family with ADNSHL. On the basis of specific segregation in the currently studied family and the general guidelines of the American College of Medical Genetics and Genomics, we argue that the TECTA c.6183G>T variant should be considered a likely pathogenic cause of ADNSHL. This report adds to the knowledge on the rare c.6183G>T missense variant, which affects the immediate vicinity of the ZP domain in TECTA. Our findings highlight the importance of clinical evaluation in patients with familial HL and of studying family segregation when assessing the pathogenicity of a variant.

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