Asgharzade Samira, Tabatabaiefar Mohammad Amin, Modarressi Mohammad Hossein, Ghahremani Mohammad Hossein, Reiisi Somayeh, Tahmasebi Parisa, Abdollahnejad Fatemeh, Chaleshtori Morteza Hashemzadeh
Department of Molecular Medicine School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran; Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Int J Pediatr Otorhinolaryngol. 2017 Jan;92:88-93. doi: 10.1016/j.ijporl.2016.11.010. Epub 2016 Nov 15.
Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder. Alpha-tectorin, which is encoded by the TECTA gene, is a non-collagenous component of the tectorial membrane in the inner ear defect of which leads to moderate to severe hearing loss (HL).
25 unrelated Iranian multiplex ARNSHL families, negative for GJB2 mutations, were recruited in this study. Clinical inspections including audiometric and otologic examinations ruled out syndromic forms. Genetic linkage analysis was performed using six short tandem repeat markers closely linked to DFNB21. Haplotype and LOD score analysis were used to confirm possible linkage. All coding exons of TECTA were subject to DNA sequencing in the linked family.
A novel homozygous variant (c.734G > A) was found in exon 5 of the TECTA gene in one family leading to a nonsense mutation (p.W245×). It co-segregated with HL in the family. This variant was not detected in 50 controls. All affected individuals in the family had moderate to severe HL. It full filled the criteria of a pathogenic variant.
Our data confirms the phenotype-directed genotyping for DFNB21 deafness against the typical profound HL phenotype seen in the most families segregating ARNSHL. We recommend mutation screening of TECTA in ARNSHL families segregating moderate to severe HL phenotype.
常染色体隐性非综合征性听力损失（ARNSHL）是一种具有遗传异质性的感音神经性疾病。由TECTA基因编码的α-耳畸蛋白是内耳盖膜的一种非胶原成分，其缺陷会导致中度至重度听力损失（HL）。
本研究招募了25个与GJB2突变阴性的不相关伊朗多重ARNSHL家系。包括听力测定和耳科检查在内的临床检查排除了综合征形式。使用与DFNB21紧密连锁的六个短串联重复标记进行遗传连锁分析。单倍型和LOD评分分析用于确认可能的连锁关系。对连锁家系中TECTA的所有编码外显子进行DNA测序。
在一个家系的TECTA基因第5外显子中发现了一个新的纯合变异（c.734G>A），导致无义突变（p.W245×）。它在家系中与HL共分离。在50名对照中未检测到该变异。该家系中所有受影响个体均有中度至重度HL。它符合致病变异的标准。
我们的数据证实了针对DFNB21耳聋的表型导向基因分型，与大多数分离ARNSHL的家系中所见的典型重度HL表型不同。我们建议对分离中度至重度HL表型的ARNSHL家系进行TECTA突变筛查。
