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

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/m²). 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/m²). This case describes a range of metabolic findings in a patient carrying a GRIA3 duplication.