Chromosome subtelomeric analysis by FISH in patients with mental retardation

Abstract

To assess subtelomeric chromosome anomalies in patients with idiopathic mental retardation (MR). Subtelomeric screening was performed in 46 patients with undiagnosed mental retardation. The patients were selected based on the following criteria: (1) MR with two or more of the following conditions: dysmorphic features, prenatal growth retardation, postnatal growth abnormalities, a suggestive family history; (2) chromosome karyotype at the level >450 bands being normal; (3) exclusion of other identified genetic or environmental diagnosis. Fluorescence in situ hybridization (FISH) was performed using ToTelVysion DNA probes. Abnormal findings were confirmed by FISH with a specific subtelomeric probes and family studies were carried out to determine its inheritance. Clinically significant aberrations were detected in two cases with 6q and 2q terminal microdeletion. The deletion in one case was inherited from a similarly affected father. Subtle chromosomal subtelomeric abnormalities occurred with a frequency of 7.6% in children with moderate to severe mental retardation and of 3.0% in the children with mild retardation. The results suggest that cryptic abnormalities of the ends of chromosomes might represent a significant cause of mental retardation, and screening for subtelomeric rearrangements might be warranted in children with unexplained mental retardation.