临床孤立性听力损失作为PEX26相关过氧化物酶体生物发生障碍的轻度表型：一例病例报告、文献综述及计算机模拟分析

文献信息

中文摘要

背景： 过氧化物酶体疾病由过氧化物酶体功能受损引起，表现出广泛的临床表型谱。近期研究表明，PEX26突变约占病例的3%，其导致的临床谱从严重的新生儿型到临床孤立性听力损失（CIHL）——一种近期被认识的表型——不等。
方法： 对一名无其他临床表现的伊朗男性双侧感音神经性听力损失患者进行全外显子组测序和拷贝数变异（CNV）分析，以确定其遗传基础。同时进行了全面的文献综述，以将我们的发现置于背景中。
结果： 我们在先证者中鉴定出一个纯合PEX26变异c.266G > T（p.Gly89Val），该变异在家系中与疾病共分离。计算机模拟分析提供了支持该变异可能具有有害作用的计算证据。通过文献综述共鉴定出61例已报道的PEX26相关疾病病例，其中Arg98Trp最为常见（30%）。大多数变异聚集于外显子2-3和胞质结构域。
结论： 本研究在一个评估时无明显的听觉外表现的听力损失家系中鉴定出一个新的PEX26变异，并提供了初步证据提示PEX26功能障碍与听觉表型之间可能存在关联。

英文摘要

BACKGROUND: Peroxisome disorders result from impaired peroxisomal function and exhibit a broad spectrum of clinical phenotypes. Recent studies suggest that mutations in PEX26, accounting for approximately 3% of cases, contribute to a clinical spectrum ranging from severe neonatal forms to clinically isolated hearing loss (CIHL), a recently recognized phenotype.
METHODS: Whole-exome sequencing and copy-number variation (CNV) analysis were performed to identify the genetic basis of bilateral SNHL without any other clinical manifestations in an Iranian man. A comprehensive literature review was also conducted to contextualize our findings.
RESULTS: We identified a homozygous PEX26 variant, c.266G > T (p.Gly89Val), in the proband, segregating with the disease in the family. In silico analyses provided computational evidence supporting a potentially deleterious effect of the variant. Sixty-one reported cases of PEX26-related disorders were identified through a literature review, with Arg98Trp being the most frequent (30%). Most variants clustered in exons 2-3 and the cytoplasmic domain.
CONCLUSION: This study identifies a novel PEX26 variant in a family with hearing loss without overt extra-auditory manifestations at the time of evaluation and provides preliminary evidence suggesting a possible association between PEX26 dysfunction and auditory phenotype.