The use of Multiplex Ligation Dependent Probe Amplification (MLPA) in the detection of copy number variance of subtelomeric regions in idiopathic intellectual disability

Abstract

Intellectual disability (ID)is characterized by significant limitations in intellectual functioning and adaptive behavior and is often associated with developmental delay and multiple congenital anomalies. It has a major effect on the life of the affected person his family and the society and it is a frequently occurring disorder. The study of the intellectual disability is complicated because of the high clinical and genetic heterogeneity. Intellectual disability can be caused by genetic defects as well as environmental causes affecting the development and function of the nervous system. Although Intellectual disability can be caused by environmental insults but a large proportion is caused by genetic abnormalities. Still, around 60% of cases of Intellectual disability do not have a known etiology. Systematic assessment of a child with intellectual disability has many steps starting with detailed history, full physical examination, and screening laboratory testing. Karyotype considered the traditional diagnostic test for genetic evaluation in patients with idiopathic non-syndromic intellectual disability. Other tests include screening tests, metabolic tests, TORCH screens, and neuroimaging, all of which have limited diagnostic value. Chromosomal analysis using the classical cytogenetic studies is considered the standard method for investigating syndromes suspected to have a chromosomal etiology but it cannot detect chromosomal imbalances smaller than 5-10 Mb. So, many subtelomeric copy number variance especially those close to the telomeres cannot be detected by conventional karyotype. Subtelomeric regions are gene-rich parts of the chromosome. Microdeletions and subtelomeric rearrangements that disrupt genes in the telomeric region can cause intellectual disability. The identification of subtelomeric copy number variance as the genetic