GRIA3 Duplication at Xq25 in a Young Adult Male With Profound Intellectual Disability and Morbid Obesity: A Case Report

We report a 22‐year‐old Japanese male with profound intellectual disability (IQ 16), autism spectrum disorder (ASD), and drug‐controlled epilepsy referred for obesity management (height 182.7 cm, weight 139.7 kg, and BMI 41.9 kg/m 2 ). Clinical features included brachycephaly, deep‐set eyes, prominent supraorbital ridges, bitemporal narrowing, broad nasal root, hypotonia, hyporeflexia, and sleep–wake cycle disorder. Chromosomal microarray analysis (CMA) performed by SRL Inc. (Tokyo, Japan) using an Affymetrix‐based platform (specific array model not disclosed by the laboratory) identified a duplication at Xq25 (minimum interval: chrX:121,515,588–122,689,238; maximum interval: chrX:121,468,613–122,733,639; GRCh37/hg19; arr[GRCh37] Xq25 (121,515,588_122,689,238) × 2) encompassing the entire GRIA3 gene, classified as a variant of uncertain significance (VUS). The duplicated interval did not encompass STAG2 . Parental genetic testing was declined and exome or genome sequencing was not performed; an alternative molecular diagnosis cannot be excluded. Comorbid findings included Grade 2 hypertension (161/99 mmHg), hemoglobin elevation (17.2 g/dL) possibly consistent with sleep‐disordered breathing (not formally evaluated), hepatic steatosis on ultrasonography, splenomegaly, and hyperuricemia. Progressive weight gain had begun at approximately 9 years of age, preceding antipsychotic and antiepileptic polypharmacy by approximately 8 years. Dietary and physical activity guidance without pharmacotherapy resulted in an approximately 4‐kg weight reduction over 4 months (BMI 40.6 kg/m 2 ). This case describes a range of metabolic findings in a patient carrying a GRIA3 duplication.