A novel recessive PDZD7 bi-allelic mutation in an Iranian family with non-syndromic hearing loss

Hossein Fahimi,Farshid Parvini,Sadaf Noavar,Samira Behroozi

doi:10.1186/s12920-021-00884-4

Abstract

BackgroundAutosomal recessive non-syndromic hearing loss (ARNSHL) is genetically and phenotypically heterogeneous with over 110 genes causally implicated in syndromic and non-syndromic hearing loss. Here, we investigate the genetic etiology of deafness in two GJB2 and GJB6 negative patients presenting with pre-lingual, progressive, severe hearing loss.MethodsTargeted exome sequencing (TES) using Next Generation Illumina Sequencing was used to analyze the exonic and some other important genomic regions of 154 genes in the proband. Subsequently, the mutation found was confirmed by Sanger sequencing in other affected sibling and healthy family members. The possible impact of the reported mutation on the corresponding protein was also evaluated by using bioinformatics tools. Moreover, the affected patients underwent audiological and ophthalmic evaluations.ResultsTES identified a novel homozygous missense mutation c.251T>C (p.I84T) in exon 3 of PDZD7 gene. In addition, segregation and phenotype-genotype correlation analysis as well as in-silico evaluations confirmed the autosomal recessive inheritance pattern and disease-causing nature of mutation found.ConclusionsIn overall, our finding could expand the pathogenic mutations spectrum and strengthens the clinical importance of the PDZD7 gene in ARNSHL patients. It can also aid to conduct genetic counseling, prenatal diagnosis and clinical management of these types of genetic disorders.

Highlights

Autosomal recessive non-syndromic hearing loss (ARNSHL) is genetically and phenotypically heterogeneous with over 110 genes causally implicated in syndromic and non-syndromic hearing loss
At the present research we explored the molecular mechanism of ARNSHL in two affected patients from a single family
Regarding to proband who was negative for gap junction beta-2 protein (GJB2) and gap junction beta 6 protein (GJB6) genes mutations, he was investigated by Targeted exome sequencing (TES) technique

Summary

Introduction

Autosomal recessive non-syndromic hearing loss (ARNSHL) is genetically and phenotypically heterogeneous with over 110 genes causally implicated in syndromic and non-syndromic hearing loss. Hearing loss (HL) is a most common sensori-neural disorder which is clinically and genetically heterogeneous This defect is categorized in two types, syndromic (30%) and non-syndromic (70%) [1]. Patients who Fahimi et al BMC Med Genomics (2021) 14:37 These two proteins are scaffolding proteins that give rise to autosomal recessive non-syndromic hearing loss (ARNSHL) and Usher syndrome(USH) disorders when mutated [5,6,7]. Defects in these proteins can damage hearing and vision. It has been reported that dysfunction or mutations of PDZD7 results in Usher syndrome type 2 (USH2) [5] and ARNSHL [12, 14,15,16]

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