Genetic counseling for patients with nonsyndromic hearing impairment directed by gene analysis

Abstract

The aim of the present study was to investigate the genetic etiology of patients with nonsyndromic hearing impairment through gene analysis, and provide accurate genetic counseling and prenatal diagnosis for deaf patients and families with deaf children. Previous molecular etiological studies have demonstrated that the most common molecular changes in Chinese patients with nonsyndromic hearing loss (NSHL) involved gap junction protein β 2, solute carrier family 26, member 4 (SLC26A4), and mitochondrial DNA 12S rRNA. A total of 117 unrelated NSHL patients were included. Mutation screening was performed by Sanger sequencing in GJB2, 12S rRNA, and the hot-spot regions of SLC26A4. In addition, patients with a single mutation of SLC26A4 in the hot-spot regions underwent complete exon sequencing to identify a mutation in the other allele. A total of 36 of the 117 deaf patients were confirmed to have two pathogenic mutations, which included 4 deaf couples, husband or wife in 11 deaf couples and 17 deaf individuals. In addition, prenatal diagnoses was performed in 7 pregnant women at 18–21 weeks gestation who had previously given birth to a deaf child, and the results showed that two fetal genotypes were the same as the proband's genotypes, four fetuses carried one pathogenic gene from their parents, and one fetus was identified to have no mutations. Taken together, the genetic testing of deaf patients can provide reasonable guidance to deaf patients and families with deaf children.

Increased diagnostic yield by reanalysis of data from a hearing loss gene panel

“…Congenital hearing loss affects approximately 1–2 infants out of every 1000, with 50% of the cases resulting from genetic factors [1]. Molecular diagnosis of hearing loss can help direct the genetic counseling and clinical management of probands and their family members [2]. One of the molecular testing methods used to diagnose hearing loss is Sanger sequencing.…”

Gene mutation analysis and genetic counseling for patients with non‑syndromic hearing loss in Linyi region

“…Up to now, hundreds of genes causing hereditary hearing loss have been identified. Most of NSHL are induced by mutations in the four genes including GJB2, SLC26A4 , mtDNA 12SrRNA and GJB3 (5–9). The findings provide theoretic basis for the implementing of prenatal diagnosis of deafness genes.…”

“…It is reported that 50% of deafness is associated with genetic factors, of which 70% are classified into non-syndromic hearing loss (NSHL), and approximately 80% of NSHL are caused by autosomal recessive inheritance (3,4). Previous molecular etiology studies have shown that four NSHL genes including gap junction β-2 ( GJB2 , OMIM: 121011), GJB3 (OMIM: 603324), solute carrier family 26, member 4 ( SLC26A4 , OMIM: 605646) and mitochondrial deoxyribonucleic acid 12SrRNA (mtDNA 12SrRNA , OMIM: 561000) are most common (5–9). Therefore, mutation screening of the four genes in people provides an effective method for the diagnosis of hearing loss.…”

Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative Challenge

“…Even more important is the genetic investigation in case of hearing loss occurring in an inbred family, as it increases the prevalence of recessive forms [30] . The genetic evaluation is often long and difficult and it is based on genetic tests performed in programmed stages, on the basis of clinical suspects [18,36,72,73] . The first step is always represented by a clinical genetic evaluation; therefore, in order to plan the appropriate molecular studies, auxologic parameters and family tree are registered [69] ; facial dysmorphisms and major (such as labiopalatoschisis) and minor anomalies (such as little auricle, fifth finger clinodactily, pit, tag, renal malformations, branchial arch development anomalies) are searched [18,36] .…”