De novo missense variant in GRIA2 in a patient with global developmental delay, autism spectrum disorder, and epileptic encephalopathy
De novo missense variant in GRIA2 in a patient with global developmental delay, autism spectrum disorder, and epileptic encephalopathy
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DOI：
10.1101/mcs.a006172
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发表时间：
2022-06-01
影响因子：
1.8
通讯作者：
Wilson, Richard K.
中科院分区：
文献类型：
--
作者：
Latsko, Maeson S.;Koboldt, Daniel C.;Wilson, Richard K.
从头开始的变异越来越多地被认为是早期婴儿癫痫脑病的常见原因。我们报告一位4岁男性，以癫痫发作、自闭症谱系障碍和全球发育迟缓为特征。对先证者及其未受影响的父母进行全基因组测序，发现了GRIA2(C.1589A>；T；p.Lys530Met；ENST00000264426.14)中一种新的从头开始的错义变体。GRIA2基因的变异最近被报道导致一种常染色体显性神经发育障碍伴语言障碍和行为异常(OMIM；MIM#618917)，这种疾病的特征是智力残疾和发育迟缓，癫痫发作是其常见特征。在我们的患者中发现的从头变异体映射到AMPA受体的关键配体结合域的边缘，以前没有在gnomAD或其他公共数据库中报道，使其成为新的。我们的发现为这位患者提供了一个长期寻求的诊断，并支持GRIA2与一种显性神经发育障碍之间的联系。
De novo variants are increasingly recognized as a common cause of early infantile epileptic encephalopathies. We present a 4-yr-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.