一个具有全球发育迟缓的伊朗-阿塞拜疆-土耳其家族的新TRIT1突变的鉴定

IF 1.6 4区 医学 Q3 DEVELOPMENTAL BIOLOGY
Fatemeh Beyad, Mortaza Bonyadi, Mohammad Barzegar
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引用次数: 0

摘要

全球发育迟缓(GDD)和智力残疾(ID)影响多达3%的儿科人口,其多因素病因使遗传鉴定复杂化。迄今为止,有超过400个基因与GDD有关。在这里,我们报告了一个新的纯合剪接受体变异,NC_000001.11(NM_017646.6):c.1235-3C>;G,在TRIT1基因中,通过生物信息学分析被归类为“可能致病”。先证患者为一名5岁男性,来自一个近亲家庭,自6个月以来表现为严重的GDD、小头畸形、进行性痉挛、挛缩、畸形特征(低耳、高弓腭、猿类皱痕和尿道下裂)和难治性癫痫发作(局灶性运动性阵挛、全身性肌阵挛和强直性)。脑MRI显示非特异性萎缩,而代谢、实验室和电生理评估无显著差异。为了进一步评估该变异的频率,我们筛选了430名来自同一种族的健康个体,没有发现该变异的发生。值得注意的是,尽管该基因座在gnomAD、1000基因组计划、Genome Asia、GME Variome和Iranome等数据库中有覆盖,但尚未在任何已发表的人口数据库中记录该变异。综上所述,这些发现有力地支持了该变异的潜在致病性。此外,该家族后续妊娠的产前诊断结果显示胚胎为杂合突变。婴儿出生了,后续研究表明她很健康,在她患病的哥哥身上没有观察到任何临床表现。这进一步支持了该变异“可能致病”的分类。“这项研究扩大了trit1相关疾病的表型谱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of a Novel TRIT1 Mutation in a Consanguineous Iranian–Azeri–Turkish Family With Global Developmental Delay

Global developmental delay (GDD) and intellectual disability (ID) affect up to 3% of the paediatric population, with a multifactorial aetiology that complicates genetic identification. To date, over 400 genes have been implicated in GDD. Here, we report a novel homozygous splice acceptor variant, NC_000001.11(NM_017646.6):c.1235-3C>G, in the TRIT1 gene, classified as ‘likely pathogenic’ through bioinformatics analysis. The proband, a 5-year-old male from a consanguineous family, presented with severe GDD, microcephaly, progressive spasticity, contractures, dysmorphic features (low-set ears, high-arched palate, simian creases and hypospadias), and refractory seizures (focal motor clonic, generalized myoclonic, and tonic) since 6 months of age. Brain MRI revealed nonspecific atrophy, while metabolic, laboratory and electrophysiological evaluations were unremarkable. To further assess the variant's frequency, we screened 430 healthy individuals from the same ethnic group and found no occurrences of the variant. Notably, this variant has not been documented in any published population databases, including gnomAD, the 1000 Genomes Project, Genome Asia, GME Variome and Iranome, despite coverage of the locus in these databases. Taken together, these findings strongly support the potential pathogenicity of the variant. In addition, the prenatal diagnosis results from the subsequent pregnancy in this family showed that the embryo was heterozygous for the mutation. The baby was born, and follow-up studies indicated that she was healthy, with no clinical manifestations observed in her affected brother. This further supports the classification of the variant as ‘likely pathogenic.’ This study expands the phenotypic spectrum of TRIT1-related disorders.

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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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