Detection of cryptic telomeric chromosomal abnormalities in children with idiopathic mental retardation by fluorescence in situ hybridization [FISH]

ABSTRACT

The cause of mental retardation, present in approximately 3% of school age children is unexplained in the majority of cases. Cryptic rearrangements involving the telomeres [the distal ends of chromosomes] are thought to account for a substantial number of patients with unexplained mental retardation and multiple congenital anomalies, although the exact incidence of these rearrangements is still unclear. With the advent of chromosome-specific telomeric probes and the use of fluorescence in situ hybridization [FISH], it is now possible to identify submicroscopic rearrangements of the distal ends of chromosomes that may otherwise go undetected using conventional cytogenetic studies. A group of 25 children with idiopathic mental retardation [IQ < 70] and their parents have been investigated to determine the frequency of submicroscopic telomeric rearrangements associated with idiopathic mental retardation. Fifteen healthy children [IQ >70] served as a control group. We have detected two cryptic telomeric abnormalities among children with idiopathic mental retardation. The mother of proband 1 has been found to have cryptic abnormality while the parents of proband 2 were found to have normal chromosomes, suggesting that cryptic subtelomevic rearrangements may be inherited or may be de novo mutation. This study describes a sensitive approach to the diagnosis of cryptic abnormalities between the G band negative ends of chromosomes and confirms the significant contribution of cryptic telomeric rearrangements to idiopathic mental retardation