Yavas Cüneyd, Dogan Mustafa, Ozgor Bilge, Akbulut Ekrem, Eroz Recep
Department of Molecular Biology and Genetics Biruni University, Istanbul, Turkiye.
Basaksehir Cam and Sakura City Hospital, Genetic Diseases Assessment Center, Istanbul, Turkiye.
Brain Dev. 2025 Feb;47(1):104313. doi: 10.1016/j.braindev.2024.104313. Epub 2024 Dec 19.
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth type 2S (CMT2S) typically present before age 10. Genetic factors account for up to 50 % of neuropathies, which often display varied symptoms. Mutations in the IGHMBP2 gene are associated with both CMT2S and SMARD1, resulting in a rare clinical condition marked by axonal neuropathy, spinal muscular atrophy, respiratory distress, and muscle weakness.
Detailed family histories and medical data were collected. Segregation analysis was performed using Sanger sequencing and whole exome sequencing. Additionally, a review of molecularly confirmed patients was conducted. Protein tertiary structures expressed in the IGHMBP2 gene were tested for topological and conformational changes using modeling programs and in-silico tools.
We identified a novel homozygous nonsense mutation (c.2568_2569del p.Gly857Alafs*27) in a family with a member showing neuropathy. This report details the clinical and genetic findings of the affected individuals, including a Turkish patient with neuropathy, and compares them with literature cases.
Understanding the clinical impact of the (c.2568_2569del p.Gly857Alafs*27) mutation will enhance our knowledge of IGHMBP2 gene defects role in neuropathy. This study aims to highlight this severe recessive disease caused by pathogenic IGHMBP2 gene mutations and to examine the mutation spectrum and phenotype differences.
1型伴有呼吸窘迫的脊髓性肌萎缩症（SMARD1）和2S型夏科-马里-图斯病（CMT2S）通常在10岁前发病。遗传因素在神经病变中占比高达50%，这些病变常常表现出多样的症状。IGHMBP2基因突变与CMT2S和SMARD1均相关，导致一种以轴索性神经病变、脊髓性肌萎缩、呼吸窘迫和肌肉无力为特征的罕见临床病症。
收集详细的家族病史和医学数据。使用桑格测序和全外显子组测序进行分离分析。此外，对分子确诊的患者进行了回顾。使用建模程序和计算机模拟工具测试IGHMBP2基因中表达的蛋白质三级结构的拓扑和构象变化。
我们在一个有成员表现出神经病变的家族中鉴定出一种新的纯合无义突变（c.2568_2569del p.Gly857Alafs*27）。本报告详细描述了受影响个体的临床和遗传发现，包括一名患有神经病变的土耳其患者，并将他们与文献中的病例进行了比较。
了解（c.2568_2569del p.Gly857Alafs*27）突变的临床影响将增进我们对IGHMBP2基因缺陷在神经病变中作用的认识。本研究旨在突出由致病性IGHMBP2基因突变引起的这种严重隐性疾病，并研究突变谱和表型差异。
