新见解遗传痉挛性截瘫在印度的遗传概况

IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Journal of neurogenetics Pub Date : 2022-01-02 DOI:10.1080/01677063.2022.2064463
Sundarapandian Narendiran, M. Debnath, S. Shivaram, Ramakrishnan Kannan, Shivani Sharma, R. Christopher, D. Seshagiri, S. Jain, M. Purushottam, Sandhya Mangalore, R. Bharath, P. Bindu, S. Sinha, A. Taly, M. Nagappa
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引用次数: 1

摘要

遗传性痉挛性截瘫(HSPs)是一组临床和遗传异质性疾病,其特征是皮质脊髓束的长度依赖性变性。印度与热休克蛋白相关的遗传数据有限。我们的目的是全面分析来自印度的一个大队列热休克综合征的表型特征和遗传基础。对HSP表型患者的临床特征、电生理和放射学异常进行评估。通过临床外显子组测序(n = 52)和靶向测序(n = 5)进行遗传分析。该队列由57个先证者组成(男:女40:17,年龄:3.5-49岁)。根据表型,该队列可分为“纯”(n = 15, 26.3%)和“复杂”(n = 42, 73.7%) HSP。脑MRI表现为胼胝体薄(10例),脑室周围高信号(20例),脑萎缩(3例),小脑萎缩(3例),弥漫性萎缩(4例)。共鉴定出40个基因的67个变异,其中包括47个新变异。48例患者(84.2%)具有先前与HSP和其他痉挛性截瘫综合征相关的基因变异(SPG基因= 24,非SPG基因= 24);在这些患者中,13名患者有一个以上的基因变异,12名患者(21.0%)有与潜在可治疗/可改变代谢疾病相关的基因变异(MTHFR = 8, MTRR = 1, ARG1 = 2和ABCD1 = 1)。在9例患者中,没有发现与痉挛性截瘫表型相关的遗传变异。因此,目前来自印度的研究强调了HSP患者的表型复杂性和遗传变异谱,包括那些与代谢可改变疾病有关的患者。它为开展功能研究提供了一个平台,以验证新变体和不确定意义变体的因果作用。
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Novel insights into the genetic profile of hereditary spastic paraplegia in India
Abstract The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Patients with HSP phenotype were evaluated for their clinical features, electrophysiological and radiological abnormalities. Genetic analyses were carried out by clinical exome sequencing (n = 52) and targeted sequencing (n = 5). The cohort comprised of 57 probands (M:F 40:17, age: 3.5–49 years). Based on the phenotype, the cohort could be categorized as ‘pure’ (n = 15, 26.3%) and ‘complicated’ (n = 42, 73.7%) HSP. Brain MRI showed thin corpus callosum (n = 10), periventricular hyperintensities (n = 20), cerebral atrophy (n = 3), cerebellar atrophy (n = 3) and diffuse atrophy (n = 4). Sixty-seven variants representing 40 genes were identified including 47 novel variants. Forty-eight patients (84.2%) had variants in genes previously implicated in HSP and other spastic paraplegia syndromes (SPG genes = 24, non-SPG genes = 24); among these 13 had variations in more than one gene and 12 patients (21.0%) had variations in genes implicated in potentially treatable/modifiable metabolic disorders (MTHFR = 8, MTRR = 1, ARG1 = 2 and ABCD1 = 1). In nine patients, no genetic variants implicated in spastic paraplegia phenotype were identified. Thus, the present study from India highlights the phenotypic complexities and spectrum of genetic variations in patients with HSP including those implicated in metabolically modifiable disorders. It sets a platform for carrying out functional studies to validate the causal role of the novel variants and variants of uncertain significance.
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来源期刊
Journal of neurogenetics
Journal of neurogenetics 医学-神经科学
CiteScore
4.40
自引率
0.00%
发文量
13
审稿时长
>12 weeks
期刊介绍: The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms
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