Late Onset Spinal Motor Neuronopathy Is Caused by Mutation in CHCHD10
Late Onset Spinal Motor Neuronopathy Is Caused by Mutation in CHCHD10
复制标题
DOI：
10.1002/ana.24319
复制
发表时间：
2015-01-01
影响因子：
11.2
通讯作者：
Udd, Bjarne
中科院分区：
文献类型：
--
作者：
Penttila, Sini;Jokela, Manu;Udd, Bjarne
本研究对晚发性脊髓运动神经元病（LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048）的致病基因进行了研究。进行全基因组测序，以找到所有可能的致病性突变的连接区域。通过桑格sequencing.ResultsSix新的SMAJ家庭的基础上确定的独特的创始人单倍型检测到的变化进行了验证。在1个家系中，标记SHGC-106816和D22 S345之间发生了一次关键重组，将连锁区域限制在727 kb。在全基因组测序中，在CHCHD 10中鉴定了先前未知的突变c.197G>T p.G66V。结论CHCHD 10中c.197G>T p.G66V突变是引起下运动神经元综合征LOSMoN/SMAJ的原因。在本文的准备过程中，其他突变被报道会导致额颞叶痴呆-肌萎缩侧索硬化综合征，表明CHCHD 10基因对运动和认知神经元系统非常重要。神经网络2015;77：163-172
ObjectiveA study was undertaken to identify the responsible gene defect underlying late onset spinal motor neuronopathy (LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048), an autosomal dominant disease mapped to chromosome 22q11.2.MethodsThe previous genetic linkage approach by microsatellite haplotyping was continued in new families. A whole genome sequencing was performed to find all possibly pathogenic mutations in the linked area. The detected variations were verified by Sanger sequencing.ResultsSix new SMAJ families were identified based on the unique founder haplotype. A critical recombination in 1 family restricted the linked area to 727kb between markers SHGC-106816 and D22S345. In whole genome sequencing a previously unknown mutation c.197G>T p.G66V in CHCHD10 was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families.InterpretationMutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems. ANN NEUROL 2015;77:163-172