Abstract:

Intellectual Disability (ID, previously named mental retardation) is a group of common pediatric neurology disorders characterized by extensive genetic and phenotypic heterogeneity. About 25%-50% of ID was caused by genomic/genetic variants, in which genomic/genetic variants of X-chromosome are one of key pathogenic causation (25%-30%), resulting in X-linked ID (XLID). The epidemiological data showed that the male to female ratio is 1.3: 1 in ID patients. The prevalence of XLID in the whole ID population is 10%-15%, and this prevalence reaches 20%-25% in the male ID population. This sex-related differential proportion of ID may be attributed to hemizygosity of X chromosomes in males. A quick detection of genomic/genetic aberrations of X chromosome is feasible and available now due to the overwhelming development of next-generation genomic techniques and their clinical applications; in particular, whole exome sequencing, customer-designed whole genomic chip for the X chromosome, high-density target sequencing and whole X chromosomal sequencing are used widely for clinical diagnosis. In this review, we systematically summarize the pathogenicity and characteristics of X-chromosomal genomic/genetic aberrations in the male patients with ID, and how the new technologies have been used to detect X-chromosomal abnormalities. This review will help researchers understand the pathogenicity of X-chromosomal variations in male ID patients from the view of whole genome, refresh the knowledge about the genomic/genetic etiology of ID, and further provide a theoretical basis for genetic counseling and prenatal diagnosis in the future.

Key words: males with intellectual disability, X-chromosomal variations, copy number variants, single nucleotide variants