Identification of Main Genetic Causes Responsible for Non-Syndromic Hearing Loss in a Peruvian Population

Abstract

: Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population. The etiology underlying HL includes congenital and acquired causes; genetic factors are the main cause in over 50% of congenital cases. Pathogenic variants in the GJB2 gene are a major cause of congenital non-syndromic hearing loss (NSHL), while their distribution is highly heterogeneous in different populations. To the best of our knowledge, there is no data regarding the genetic etiologies of HL in Peru. In this study, we screened 133 Peruvian families with NSHL living in Lima. We sequenced both exons of the GJB2 gene for all probands. Seven probands with familial NSHL that remained negative for GJB2 variants underwent whole genome sequencing (WGS). We identified biallelic pathogenic variants in GJB2 in 43 probands; seven were heterozygous for only one allele. The c.427C>T variant was the most common pathogenic variant followed by the c.35delG variant. WGS revealed three novel variants in MYO15A in two probands, one of them was predicted to affect splicing and the others produce a premature stop codon. The Peruvian population showed a complex profile for genetic variants in the GJB2 gene, this particular profile might be a consequence of the admixture history in Peru.

Keywords: GJB2; Peruvian; hearing loss; non-syndromic.

Figure 1

a. Bar-plot of four-way admixed Peruvian individuals estimated using ADMIXTURE software at K = 4. b. The box-plot of the average ancestries in Peruvian individuals. c. Illustration of local ancestry on chromosome 13. This figure represents admixture blocks “local ancestry”, with each ancestry coded by a different color (red: African (AF), blue: European (EU), pink: American Indian (AI)), from a Peruvian individual.

Figure 2

Frequency of the haplotypes in cases positive for the c.427C>T variant.