肌张力障碍与其他神经系统疾病之间的遗传重叠：一项对1100个外显子组的研究。

Genetic overlap between dystonia and other neurologic disorders: A study of 1,100 exomes.

作者信息

Dzinovic Ivana, Boesch Sylvia, Škorvánek Matej, Necpál Ján, Švantnerová Jana, Pavelekova Petra, Havránková Petra, Tsoma Eugenia, Indelicato Elisabetta, Runkel Eva, Held Valentin, Weise David, Janzarik Wibke, Eckenweiler Matthias, Berweck Steffen, Mall Volker, Haslinger Bernhard, Jech Robert, Winkelmann Juliane, Zech Michael

机构信息

Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany; Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

出版信息

Parkinsonism Relat Disord. 2022 Sep;102:1-6. doi: 10.1016/j.parkreldis.2022.07.003. Epub 2022 Jul 18.

DOI:10.1016/j.parkreldis.2022.07.003

PMID:35872528

Abstract

INTRODUCTION

Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia.

METHODS

Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability.

RESULTS

Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia.

CONCLUSIONS

Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.

摘要

引言

尽管此前已有报道称肌张力障碍与其他神经系统疾病之间存在共同的遗传因素，但尚无探索此类关联的测序研究。在一个大型肌张力障碍队列中，我们旨在分析与肌张力障碍以外的疾病类别相关的基因中致病变异的比例。

方法

将1100例肌张力障碍索引病例中与全外显子测序诊断相关的基因发现，与针对共济失调、帕金森症、痉挛性截瘫、神经病变、癫痫和智力残疾的专家整理分子检测面板进行比较。

结果

在220例确诊患者中，21%的患者在共济失调相关基因中有变异；15%在帕金森症相关基因中有变异；15%在痉挛性截瘫相关基因中有变异；12%在神经病变相关基因中有变异；32%在癫痫相关基因中有变异；65%在智力残疾相关基因中有变异。大多数确诊表现（80%）与≥1个研究面板中列出的基因有关；71%的受累基因座在非肌张力障碍面板中发现，但不在专家整理的肌张力障碍基因列表中。