Beyond the basics: Exploring STRC-related hearing loss, a lesser-known cause of deafness in Argentina

Abstract

Genetic hearing loss (HL) affects around 1:500 newborns and is primarily non-syndromic (70%). It is an heterogeneous condition, involving 124 genes. Most cases are attributed to GJB2 and GJB6 variants. One lesser-known cause of moderate HL with autosomal recessive inheritance is STRC gene alterations. This gene is in a tandem duplicated region with the STRCP1 pseudogene. Large deletions are the most common type of STRC mutations, which may also involve the adjacent CATSPER2 gene, crucial in sperm motility, leading to Deafness-Infertility Syndrome. While some studies in patients have reported a frequency of 5%, its prevalence in Argentina remains unclear.In this study, we aimed to investigate the frequency of STRC alterations in a moderate HL cohort from Argentina. A total of 105 patients were tested. Homozygous deletions were detected by amplifying a non-polymorphic marker located exclusively between STRC and CATSPER2. Heterozygous variants were studied by MLPA. Long-Range allele-specific PCR and Sanger sequencing were used to detect SNVs.Seven of 105 unrelated cases resulted with causative STRC variants (6.7%). Some cases had homozygous deletion of STRC and CATSPER2 while others exhibited compound heterozygous deletion of STRC in trans with causative SNVs. The complexity of this region was shown in our findings, with one case presenting a deletion of STRC and duplication of the STRCP1 pseudogene, suggesting a possible mechanism of gene conversion.STRC-related hearing loss typically presents as moderate and stable, so the diagnosis could bring relief to patients concerning the evolution of the pathology as well the STRC-CATSPER2 loss modifies the clinical diagnosis of the patients to a syndromic status. This highlights the importance of accurate diagnosis for providing patients with proper genetic counseling. Our study serves as a significant precedent in the analysis of STRC-associated hearing loss in Argentina.