Abstract

Background:The etiology of mental retardation (MR) is unexplained in at least 50% of cases. Recently it was shown that subtle telomeric rearrangements may be a common cause of idiopathic mental retardation (IMR).Material/Methods: We studied 84 families with IMR and unspecific clinical features suggesting chromosomal aberration, including 59 patients with moderate to severe MR and 24 with mild MR. One healthy father of three deceased, severely MR children was also included. Fluorescence in situ hybridization (FISH) using 41 subtelomeric probes (the Chromoprobe Multiprobe[sub]®[/sub] – T System) was performed in all patients.Results: Ten (11.9%) subtle chromosome rearrangements were identified. Nine (10.7%) were subtelomeric abnormalities. Seven were familial, with six of paternal origin. All but one were products of parental balanced reciprocal translocation or inversion. Retrospective G-banding analysis showed that six of the nine rearrangements could be seen or suspected at the 450–550 band levels. Subtelomeric abnormalities were recognized in six patients with severe/moderate (including the father of children with severe MR) and in three with mild MR.Conclusions: Our results confirm previous findings on the importance of subtelomeric rearrangements in the etiology of MR. They also show the diagnostic utility of subtelomeric FISH in detecting subtle telomeric rearrangements in IMR cases. The high proportion of familial rearrangements emphasizes their importance for genetic counseling. FISH screening was more reliable and efficient in identifying subtle telomeric abnormalities than G-banding analysis. However, as many of the subtelomeric abnormalities could be detected in retrospect even at the 550 band level, high-resolution G-banding analysis should always precede subtelomere assay. This is important for a better estimation of the real frequency of cryptic subtelomeric abnormalities.

Keywords: Chromosome Aberrations, Chromosome Disorders - genetics, DNA Probes - chemistry, In Situ Hybridization, Fluorescence, Karyotyping, Mental Retardation - genetics, Telomere - genetics, Chromosome Aberrations, Chromosome Disorders - genetics, DNA Probes - chemistry, In Situ Hybridization, Fluorescence, Intellectual Disability - genetics, Karyotyping, Telomere - genetics