A novel USP27X missense variant identified in an individual with intellectual disability

Abstract

X-linked intellectual disability (XLID) is a group of neurodevelopmental disorders with genetic heterogeneity. Mutation of USP27X, a deubiquitinase encoding gene, is associated with X-linked intellectual developmental disorder-105 (XLID105), which is characterized by different combinations of impaired intellectual development (ID), developmental delay (DD), autism spectrum, attention deficit hyperactivity disorder and anxiety. Now only fourteen genetically diagnosed individuals have been reported. Here we describe a three-year boy with mild abnormal facial features, DD, severe speech delay and cognitive impairment, and ventricular septal defect. In addition, an increased nuchal translucency was observed during the fetal period. Trio whole-exome sequencing identified a novel missense variant, c.257 C > T (p.Thr86Met), in the USP27X gene (NM_001145073), which is inherited from his healthy mother and assessed to be a variant of uncertain significance. Further in vitro function study shows that this variant is detrimental to the expression and deubiquitination activity of USP27X. Our study provides more pathogenic evidences for this variant identified, and link this variant to the XLID-105 disease. In conclusion, our report expands the clinical and genetic spectrum of USP27X. Clinical trial registration: ChiCTR2000034358.