Nonamyloidogenic TTR gene variants c.76G>A and c.337-18G>C are not associated with idiopathic small-fiber neuropathy

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY European Journal of Neurology Pub Date : 2024-09-04 DOI:10.1111/ene.16461

Céline Konecki, Bruno Francou, Kenneth Chappell, Lucie Augey, Guillemette Beaudonnet, Cécile Cauquil, Dalia Dimitri-Boulos, Adeline Not, Clovis Adam, Vianney Poinsignon, Céline Verstuyft, David Adams, Andoni Echaniz-Laguna, Céline Labeyrie

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Abstract

Background and Purpose

Small-fiber neuropathy (SFN) affects only unmyelinated and thin myelinated fibers. It may be caused by amyloidogenic mutations of the transthyretin (TTR) gene, but not all TTR gene variants are pathogenic. The nonamyloidogenic c.76G>A (rs1800458) and c.337-18G>C (rs36204272) variants of TTR were recently reported to be associated with SFN. We investigated this putative association by analyzing TTR gene sequencing data retrospectively for two cohorts of patients, one with SFN and a control group.

Methods

In this retrospective single-center study, we analyzed the frequency of the c.76G>A and c.337-18G>C TTR gene variants in a cohort of patients meeting a strict definition of SFN, with or without dysautonomia, a control cohort of patients investigated for nonneurological conditions, and the gnomAD international database.

Results

We included 55 SFN patients in this study, 17 of whom had dysautonomia. The allelic frequencies of the two variants in our cohort of 55 SFN patients were 7.27% for c.76G>A TTR and 5.25% for c.337-18G>C. The frequencies of both variants were statistically similar in the 337 control patients and the gnomAD database.

Conclusions

The c.76G>A and c.337-18G>C TTR gene variants are not associated with SFN.

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非淀粉样变性 TTR 基因变异 c.76G>A 和 c.337-18G>C 与特发性小纤维神经病无关。

背景和目的：小纤维神经病（SFN）仅影响无髓鞘纤维和薄髓鞘纤维。它可能是由转甲状腺素（TTR）基因的淀粉样突变引起的，但并非所有的 TTR 基因变异都具有致病性。最近有报道称，TTR 的非淀粉样蛋白致病变体 c.76G>A (rs1800458) 和 c.337-18G>C (rs36204272) 与 SFN 相关。我们通过回顾性分析两组患者（一组为 SFN 患者，另一组为对照组）的 TTR 基因测序数据，研究了这种假定的关联性：在这项回顾性单中心研究中，我们分析了符合严格定义的 SFN 患者队列中 c.76G>A 和 c.337-18G>C TTR 基因变异的频率，无论这些患者是否伴有自主神经功能障碍，对照队列中的患者均接受了非神经系统疾病的检查，以及 gnomAD 国际数据库：本研究共纳入 55 名 SFN 患者，其中 17 人患有自主神经功能障碍。在我们的 55 名 SFN 患者队列中，c.76G>A TTR 和 c.337-18G>C 这两个变异体的等位基因频率分别为 7.27% 和 5.25%。在 337 例对照患者和 gnomAD 数据库中，这两个变异体的频率在统计学上相似：结论：c.76G>A 和 c.337-18G>C TTR 基因变异与 SFN 无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Neurology 医学-临床神经学

CiteScore

9.70

自引率

2.00%

发文量

418

审稿时长

1 months

期刊介绍： The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).