Bazazzadegan Niloofar, Babanejad Mojgan, Banihashemi Susan, Arzhangi Sanaz, Kahrizi Kimia, Booth Kevin Ta, Najmabadi Hossein
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Department of Medical and Molecular Genetics, Indiana School of Medicine, Indianapolis, IN, USA.
Arch Iran Med. 2025 Jan 1;28(1):63-66. doi: 10.34172/aim.31746.
Cytoskeletal dynamics, the interplay of actin, microtubules, and septins, is a highly coordinated and tightly regulated process. Defects in the proteins involved can result in a wide range of cellular consequences. Hearing loss is the most common sensory defect and exhibits extraordinary genetic and phenotypic heterogeneity. Currently, there are more than 170 genes casually linked to non-syndromic hearing loss (NSHL), of which more than 60 are associated with autosomal dominant inheritance. Here, we add to this growing number by implicating (OMIM # 608271), as a novel candidate gene for autosomal dominant non-syndromic hearing loss (ADNSHL). MACF1's cytoskeleton integrator function and hair cell expression pattern lead one to believe that it is a necessary protein for hair cells. Many protein domains in MACF1 allow for dynamic interaction with the cytoskeleton. A large Iranian family segregating progressive ADNSHL was recruited for this study. The proband had bilateral mild-moderate sensorineural hearing loss and was negative for mutations. After applying exome sequencing on the proband, a missense mutation c.1378C>T (p.His460Tyr) was found in and co-segregated with the hearing loss in the extended family. We speculated that mutations probably cause non-syndromic hearing loss inherited in an autosomal dominant manner. The potential functional impact of the identified variant will be investigated through further analysis.
细胞骨架动力学，即肌动蛋白、微管和隔膜蛋白之间的相互作用，是一个高度协调且受到严格调控的过程。相关蛋白质的缺陷可能导致多种细胞后果。听力损失是最常见的感觉缺陷，表现出显著的遗传和表型异质性。目前，有超过170个基因与非综合征性听力损失（NSHL）存在因果关联，其中60多个与常染色体显性遗传相关。在此，我们通过将（OMIM # 608271）作为常染色体显性非综合征性听力损失（ADNSHL）的一个新候选基因，增加了这一数量。MACF1的细胞骨架整合功能和毛细胞表达模式让人相信它是毛细胞所需的一种蛋白质。MACF1中的许多蛋白质结构域允许与细胞骨架进行动态相互作用。本研究招募了一个患有进行性ADNSHL的大型伊朗家族。先证者患有双侧轻中度感音神经性听力损失，且未检测到 突变。在先证者身上应用外显子组测序后，在 中发现了一个错义突变c.1378C>T（p.His460Tyr），并在扩展家族中与听力损失共分离。我们推测 突变可能导致以常染色体显性方式遗传的非综合征性听力损失。将通过进一步分析研究已鉴定变异的潜在功能影响。
