A Missense Variation in the KDM5C Gene Associated with X-Linked Intellectual Disability, Growth Failure, and Epilepsy

Abstract

Mutations in the lysine demethylase 5C ( KDM5C ) gene are an important cause of the syndromic Claes-Jensen type of X-linked intellectual disability and are associated with mild to severe intellectual disability. Intellectual disability is a clinically variable and genetically heterogeneous disorder characterized by limitations in both intellectual functioning and adaptive behavior, af-fecting the social and practical skills that are learned before the age of 18 years [1,2]. Intellectual disability affects 1% to 3% of the population worldwide and often coexists with other neuro-logical conditions [3]. Advances in human genetics and clinical research have led to the identification of hundreds of genes responsible for intellectual disability. Numerous studies of large cohorts of patients with intellectual disabilities have shown that the disease has a significantly higher incidence in males, indicating that X-linked gene defects are the main cause of intellectual disability [4]. Here, we report three male siblings with variations in KDM5C , c.1602G>C (p.Trp534Cys