title: Xq21.31-q21.32 duplication underlies intellectual disability in a large family with five affected males.
abstract: 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.
authors.affiliation: Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia.
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.affiliation: Department of Metabolic Diseases, King Abdulla Medical City-Madinah Maternity and Children Hospital, Almadinah Almunawwarah, Saudi Arabia.
authors.forename: Omhani I
authors.initials: OI
authors.lastname: Malibari
authors.affiliation: Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia.
authors.forename: Alia M
authors.initials: AM
authors.lastname: Al-Balawi
authors.affiliation: Prince Naif Centre for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sibtain
authors.initials: S
authors.lastname: Afzal
authors.affiliation: College of Medicine, Taibah University Almadinah Almunawwarah, Saudi Arabia.
authors.forename: Amr Elsayed Mohamed
authors.initials: AE
authors.lastname: Eldardear
authors.affiliation: Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D058674:Chromosome Duplication; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D049951:X Chromosome Inactivation; D055815:Young Adult
keywords: copy number variation; intellectual disability; x-linked