TGM6 可能不是遗传分析和功能研究导致的脊髓小脑共济失调的特定致病基因。

TGM6 might not be a specific causative gene for spinocerebellar ataxia resulting from genetic analysis and functional study.

机构信息

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.

出版信息

Gene. 2021 May 5;779:145495. doi: 10.1016/j.gene.2021.145495. Epub 2021 Feb 13.

DOI:10.1016/j.gene.2021.145495

PMID:33588035

Abstract

OBJECTIVE

To investigate whether TGM6 is a specific causative gene for spinocerebellar ataxia type 35 (SCA35).

MATERIALS AND METHODS

The next-generation sequencing (NGS) data consisted of 47 SCA, 762 non-SCA patients and 2827 normal controls were analyzed. The allele frequencies of low frequent and deleterious TGM6 variants were compared. Functional studies were performed in five widely distributed variants (V314M, R342Q, P347L, V391M, L517W).

RESULTS

Two TGM6 detrimental variants were identified in one SCA patient, 14 in non-SCA patients and 43 in normal controls, the allele frequencies of TGM6 variants did not differ among the SCA and other controls. Seven reported pathogenic variants (c.7 + 1G > T, c.331C > T, c.1171G > A, c.1478C > T, c.1528G > C, c.1550 T > G and c.1722_1724delAGA) were identified in patients with various neurologic diseases or normal controls. All the 5 widely distributed variants led to destabilization and significantly reduction of enzymatic activity of TG6 as the reported pathogenic mutations.

CONCLUSIONS

TGM6 might not be a specific causative gene for SCA35, the relevant clinical consult or diagnostic should be pay more attention.

摘要

目的

研究 TGM6 是否为脊髓小脑性共济失调 35 型（SCA35）的特异性致病基因。

材料与方法

分析了下一代测序（NGS）数据，其中包括 47 例 SCA、762 例非 SCA 患者和 2827 例正常对照。比较了低频和有害 TGM6 变异体的等位基因频率。在 5 种广泛分布的变体（V314M、R342Q、P347L、V391M、L517W）中进行了功能研究。

结果

在 1 例 SCA 患者中发现了 2 个有害 TGM6 变异体，在 14 例非 SCA 患者和 43 例正常对照中发现了 14 个，TGM6 变异体的等位基因频率在 SCA 和其他对照之间没有差异。在患有各种神经疾病的患者或正常对照中发现了 7 个报道的致病性变异体（c.7+1G>T、c.331C>T、c.1171G>A、c.1478C>T、c.1528G>C、c.1550T>G 和 c.1722_1724delAGA）。所有 5 种广泛分布的变体均导致 TG6 的稳定性降低和酶活性显著降低，与报道的致病性突变一致。