Mental retardation (MR) involves a complex collection of clinically and genetically diverse disorders. Diagnosis of MR is typically based on three main criteria: onset of symptoms before the age of 18, intellectual abilities significantly lower than average, and reduced adaptive skills. Individuals with MR tend to struggle in areas including communication, health, interpersonal/social skills, leisure, safety, self-guidance and care, school performance, and work.                     

X-linked mental retardation (XLMR) is associated with more than 200 conditions linked to >90 genes on the X chromosome. XLMR affects approximately 1/600-1/1000 males, as well as a significant number of females.   Mutations in these genes have been shown to be an underlying cause of mental retardation, which may or may not be associated with other congenital anomalies, developmental delay, autism, dysmorphism, and numerous genetic syndromes.  One of the XLMR associated genes is CUL4B.

CUL4B encodes a protein subunit that forms the Cullin-RING ubiqutin ligase complex and participates in ubiquitin-dependent protein degradation. This fundamental cellular process has been implicated in cell cycle, immune response, and development. The CUL4B gene is located at Xq24 and contains 22 exons. Missense/nonsense mutations, small and gross deletions, and splicing mutations have been reported in CUL4B. The main clinical features of patients with mutations in CUL4B include mental retardation, aggressive outbursts, tremor, central obesity, and hypogonadism (Tarpey PS et al. Am J Hum Genet. 2007;80:345-352).