Novel Pathogenic Variants in the Gene Encoding Stereocilin ( STRC ) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects

• Published in: Biomedicines Vol. 11; no. 11; p. 2943
• Main Authors: Domínguez-Ruiz, María, Ruiz-Palmero, Laura, Buonfiglio, Paula I, García-Vaquero, Irene, Gómez-Rosas, Elena, Goñi, Marina, Villamar, Manuela, Morín, Matías, Moreno-Pelayo, Miguel A, Elgoyhen, Ana B, Del Castillo, Francisco J, Dalamón, Viviana, Del Castillo, Ignacio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.10.2023
• Subjects: DFNB16; DNA sequencing; Epidemiology; Genes; Genetic aspects; genetic epidemiology; Genetics; Genomes; Genomics; Genotypes; Haplotypes; Hearing loss; Hearing protection; Multiprocessing; Mutation; non-syndromic hearing impairment; Nucleotide sequencing; Phenotypes; Siblings; stereocilin; STRC; Argentina; Spain; United States > US; non-syndromic hearing impairment; DFNB16; STRC; stereocilin; genetic epidemiology
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11112943

Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in , encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. is located in a tandem duplicated region that includes the pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving . Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype-phenotype correlation and highlight the significant contribution of mutations to moderate NSHI in the Spanish population.