Xq21.31-q21.32 duplication underlies intellectual disability in a large family with five affected males

X-linked intellectual disability is the most common form of neurological disorder in male and accounts for 5-10% of incidence in the population. Copy number variants (CNVs) have been studied extensively to identify genomic regions responsible for neurological disorders. Array CGH and SNP genotyping have identified several CNVs on X-chromosome in patients with X-linked intellectual disability. We genotyped 2.5 million SNPs in 10 individuals of a 4 generation family segregating X-linked intellectual disability using Illumina Infinium BeadChip assay. Whole genome genotyping data analysis identified a single duplication of 3.95 Mb on X-chromosome in all five affected male individuals. This CNV is inherited from a healthy mother. All five affected individuals manifest moderate to severe intellectual disability, seizures and behavioral abnormalities. X-chromosome inactivation analysis showed that X-chromosome of the mother with duplication is completely inactivated which has also been found in daughters.