De novo missense mutation in GRIA2 in a patient with global developmental delay, autism spectrum disorder, and epileptic encephalopathy.

Autor:	Latsko MS; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital., Koboldt DC; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital; daniel.koboldt@nationwidechildrens.org., Franklin SJ; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital., Hickey SE; Division of Genetic and Genomic Medicine at Nationwide Children's Hospital., Williamson RK; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital., Garner S; Division of Genetic and Genomic Medicine at Nationwide Children's Hospital., Ostendorf AP; Division of Child Neurology at Nationwide Children's Hospital., Lee K; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital., White P; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital., Wilson RK; Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2022 May 09. Date of Electronic Publication: 2022 May 09.
DOI:	10.1101/mcs.a006172
Abstrakt:	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. (Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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