First-Line Molecular Genetic Evaluation of Autosomal Recessive Non-Syndromic Hearing Loss

Özet

Objective: The aim of this study is to investigate theefficiency of a first-line molecular genetic evaluationapproach, in children with deafness.Methods: Patients who were found to have sensorineural hearing loss by age-appropriate audiologicaltests were selected for the molecular genetic evaluation. The molecular genetic evaluation was carriedout with GJB2 gene sequence analysis and mtDNAm.1555A>G mutation Restriction Fragment LengthPolymorphism (RFLP) analysis. Additionally, in asmall group of patients, hearing loss Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was done out to identify the possible role of copynumber changes.Results: In this Turkish cohort, which included 104index patients and 78 relatives, 33 (31.7%) had Pathogenic/Likely Pathogenic variants. One or more GJB2sequence variants were identified in 46 (44.1%) of the104 index patients. The homozygous c.35delG mutation by itself explained the etiology in 24% of ourARSNHL group. In one (5%) of the 20 patients ofMLPA group, a hemizygous deletion in POU3F4gene was detected.Conclusion: In our Turkish cohort, we applied afirst-line molecular genetic evaluation approachusing GJB2 gene sequence analysis and mtDNAm.1555A>G RFLP analysis. This approach revealedthe genetic etiology of 44.1% of our index patients.Additionaly, the results of hearing loss MLPA analysis revealed the limited role of copy number changesin this patient group. Furthermore, with a detailedgenotype-phenotype association workup, 2 rare casesof Deafness with Palmoplantar Hyperkeratosis andKeratitis-Ichthyosis-Deafness syndrome were reported.