To investigate the pathogenicity of the TGM6 variant for spinocerebellar ataxia 35 (SCA35), which was previously reported to be caused by pathogenic mutations in the gene TGM6.

Neurologic assessment and brain MRI were performed to provide detailed description of the phenotype. Whole-exome sequencing and dynamic mutation analysis were performed to identify the genotype.

The proband, presenting with myoclonic epilepsy, cognitive decline, and ataxia, harbored both the TGM6 p.L517W variant and expanded CAG repeats in gene ATN1. Further analysis of the other living family members in this pedigree revealed that the CAG repeat number was expanded in all the patients and within normal range in all the unaffected family members. However, the TGM6 p.L517W variant was absent in 2 affected family members, but present in 3 healthy individuals.

The nonsegregation of the TGM6 variant with phenotype does not support this variant as the disease-causing gene in this pedigree, questioning the pathogenicity of TGM6 in SCA35.

研究TGM6变异体对脊髓小脑性共济失调 35 (SCA35) 的致病性，此前有报道称其是由基因TGM6的致病性突变引起的。

进行神经系统评估和脑部 MRI 以提供对表型的详细描述。进行全外显子组测序和动态突变分析以鉴定基因型。

先证者出现肌阵挛性癫痫、认知能力下降和共济失调，同时携带TGM6 p.L517W 变异体和基因ATN1中扩展的 CAG 重复序列。对该谱系中其他在世家庭成员的进一步分析显示，所有患者的 CAG 重复数均增加，所有未受影响的家庭成员均在正常范围内。然而，TGM6 p.L517W 变体在 2 名受影响的家庭成员中不存在，但在 3 名健康个体中存在。

TGM6变异与表型的非分离不支持该变异作为该谱系中的致病基因，质疑TGM6在 SCA35 中的致病性。