一名患有全面发育迟缓、自闭症谱系障碍和癫痫性脑病的患者体内的 GRIA2 发生了新的错义突变。

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-05-09 DOI:10.1101/mcs.a006172
Maeson S Latsko, Daniel C Koboldt, Samuel J Franklin, Scott E Hickey, Rachel K Williamson, Shannon Garner, Adam P Ostendorf, Kristy Lee, Peter White, Richard K Wilson
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引用次数: 0

摘要

新发变异越来越被认为是早期婴儿癫痫性脑病的常见病因。我们报告了一名 4 岁男性癫痫性脑病患者,其特征为癫痫发作、自闭症谱系障碍和全面发育迟缓。对该患者及其未受影响的父母进行的全基因组测序发现,GRIA2存在一个新的从头错义变异(c.1589A>T; p.Lys530Met; ENST00000264426.14)。最近有报道称,GRIA2基因的变异可导致一种常染色体显性神经发育障碍,并伴有语言障碍和行为异常(OMIM; MIM #618917),这种疾病以智力障碍和发育迟缓为特征,癫痫发作是其常见特征。在我们的患者身上发现的新变异映射到了 AMPA 受体的一个关键配体结合域的边缘,以前在 gnomAD 或其他公共数据库中都没有报道过,因此具有新颖性。我们的研究结果为这名患者提供了一个寻找已久的诊断结果,并支持了 GRIA2 与显性神经发育障碍之间的联系。
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De novo missense mutation in GRIA2 in a patient with global developmental delay, autism spectrum disorder, and epileptic encephalopathy.

De novo variants are increasingly recognized as a common cause of early infantile epileptic encephalopathies. We present a 4-year-old male with epileptic encephalopathy characterized by seizures, autism spectrum disorder, and global developmental delay. Whole genome sequencing of the proband and his unaffected parents revealed a novel de novo missense variant in GRIA2 (c.1589A>T; p.Lys530Met; ENST00000264426.14). Variants in the GRIA2 gene were recently reported to cause an autosomal dominant neurodevelopmental disorder with language impairments and behavioral abnormalities (OMIM; MIM #618917), a condition characterized by intellectual disability and developmental delay in which seizures are a common feature. The de novo variant identified in our patient maps to the edge of a key ligand binding domain of the AMPA receptor and has not been previously reported in gnomAD or other public databases, making it novel. Our findings provided a long-sought diagnosis for this patient and support the link between GRIA2 and a dominant neurodevelopmental disorder.

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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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