Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
BMC Med Genomics. 2021 Feb 2;14(1):37. doi: 10.1186/s12920-021-00884-4.
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. Here, we investigate the genetic etiology of deafness in two GJB2 and GJB6 negative patients presenting with pre-lingual, progressive, severe hearing loss.
Targeted 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.
TES 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.
In 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.
常染色体隐性非综合征型听力损失（ARNSHL）在遗传和表型上具有异质性，超过 110 个基因与综合征型和非综合征型听力损失有关。在这里，我们研究了两名 GJB2 和 GJB6 阴性、表现为语前、进行性、严重听力损失的耳聋患者的遗传病因。
使用下一代 Illumina 测序的靶向外显子组测序（TES）用于分析先证者 154 个基因的外显子和一些其他重要的基因组区域。随后，通过 Sanger 测序在其他受影响的同胞和健康家庭成员中证实了发现的突变。还使用生物信息学工具评估了报告的突变对相应蛋白的可能影响。此外，受影响的患者接受了听力和眼科评估。
TES 鉴定了 PDZD7 基因外显子 3 中一个新的纯合错义突变 c.251T>C（p.I84T）。此外，分离和表型-基因型相关性分析以及计算机模拟评估证实了所发现的突变的常染色体隐性遗传模式和致病性质。
总的来说，我们的发现可以扩展致病突变谱，并加强 PDZD7 基因在 ARNSHL 患者中的临床重要性。它还可以帮助进行遗传咨询、产前诊断和这些类型的遗传疾病的临床管理。
