RESUMEN
Lysine-specific demethylase 6B (KDM6B) demethylates trimethylated lysine-27 on histone H3. The methylation and demethylation of histone proteins affects gene expression during development. Pathogenic alterations in histone lysine methylation and demethylation genes have been associated with multiple neurodevelopmental disorders. We have identified a number of de novo alterations in the KDM6B gene via whole exome sequencing (WES) in a cohort of 12 unrelated patients with developmental delay, intellectual disability, dysmorphic facial features, and other clinical findings. Our findings will allow for further investigation in to the role of the KDM6B gene in human neurodevelopmental disorders.
Asunto(s)
Variación Genética , Histona Demetilasas con Dominio de Jumonji/genética , Trastornos del Neurodesarrollo/genética , Adolescente , Preescolar , Estudios de Cohortes , Femenino , Humanos , MasculinoRESUMEN
A 55-yr-old male with severe intellectual disability, behavioral problems, kyphoscoliosis, and dysmorphic features was referred for a genetic evaluation. Chromosomal microarray, RASopathy gene panel, mitochondrial sequencing, and fragile X testing were all negative. Subsequent whole-exome sequencing revealed a heterozygous, truncating variant in the AHDC1 gene, consistent with a diagnosis of Xia-Gibbs syndrome (XGS). Review of his clinical history showed many classic dysmorphic and clinical features of XGS, but no major health issues in adulthood other than intellectual disability. This individual is the oldest published XGS case to date, demonstrates the wide phenotypic spectrum of the disorder, and provides information on the condition's natural history. As more adults undergo genomic studies, we will continue to learn about the adult phenotypes of genetic conditions typically diagnosed in the pediatric setting.