A novel missense variant in OTUD5 causes X-linked multiple congenital anomalies-neurodevelopmental syndrome

Background: The OTUD5 gene encodes a deubiquitinating enzyme (DUB) of the OTU family. Variants of OTUD5 are associated with X-linked multiple congenital anomalies-neurodevelopmental syndrome (MCAND). The case described in this study expands the clinical and molecular spectrum of OTUD5.Methods: Trio-based clinical exome sequencing (trio-CES) was performed on a Chinese boy with a clinical phenotype and both of his parents. Sanger sequencing was employed for validation of the variant detected.Results: The patient presented with characteristic facial features, intellectual disability, motor/language/cognitive, and global developmental delays, limb contractures, and kidney abnormalities, and trio-CES identified a de novo missense variant, c.1305T>A, of the OTUD5 gene.Discussion: We describe OTUD5 gene variation in the Chinese population, with the first report of this variant. Additionally, we provide a comprehensive summary of all published cases of MCAND to date, in order to elucidate the primary clinical features of the syndrome and the variability in phenotype severity. This case expands the genetic and clinical phenotypic spectrum of OTUD5-associated MCAND.