Subtelomeric rearrangements: results from a study of selected and unselected probands with idiopathic mental retardation and control individuals by using high-resolution G-banding and FISH

Abstract

The cause of mental retardation, present in approximately 3% of the population, is unexplained in the majority of cases. Recent reports have suggested that cryptic telomeric rearrangements resulting in segmental aneuploidy and gene-dosage imbalance might represent a significant cause of idiopathic mental retardation (IMR). Two groups of patients with unexplained developmental delay (unselected and selected) and a group of control individuals have been investigated to determine the frequency of submicroscopic telomeric rearrangements associated with IMR and the frequency within the normal population. In contrast to current thinking, our data have shown that true cryptic telomeric rearrangements are not a significant cause of IMR. No fully cryptic abnormalities were detected in our IMR groups, although a semi-cryptic unbalanced telomeric translocation was identified in one selected patient by high-resolution G-band analysis. This abnormality was confirmed and characterised by fluorescence in situ hybridisation (FISH) with telomere-specific probes. A further 13 cytogenetically detected subtle terminal rearrangements were characterised by using multi-telomere FISH. Seven of these had previously been reported as normal, three of which were shown to be interstitial deletions. These cases illustrate the importance of high-resolution analysis to exclude subtle but cytogenetically visible abnormalities prior to subtelomere FISH screening when determining the frequency of cryptic telomeric rearrangements. Unexpectedly, two cryptic telomeric abnormalities were detected among our control individuals, suggesting that submicroscopic telomeric abnormalities may be a not uncommon finding in the general population. Hence, our data have important implications when defining the significance of cryptic telomeric rearrangements detected during screening programmes.

β-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation

“…Most subtelomeric exchanges are phenotypically silent. 62,64,65 However, several studies have implicated subtelomeric deletions as a common cause of idiopathic mental retardation. [66][67][68][69] Subtelomeric deletions of a 3.3 kb repeat array on 4qter can also lead to facioscapulohumeral muscular dystrophy or FSHD.…”

Clinical Genetic Evaluation of the Child With Mental Retardation or Developmental Delays

“…[37][38][39][40][41][42][43][44] Since a complete set of FISH probes has become available clinically, the utility of these probes has been demonstrated by the numerous reports of patients with mental retardation who have had a previously normal routine karyotype, suggesting that subtelomeric abnormalities (deletions or duplications of chromosome regions) are second only to Down syndrome as the most common cause of mental retardation. 41,45 Some deletions and duplications of clinically significant chromosome material at the telomeres are not visible by standard karyotype analytic techniques; these are often referred to as "cryptic" subtelomeric chromosome anomalies (ie, they are not detectable by routine cytogenetic testing).…”

Practice parameter: Evaluation of the child with global developmental delay [RETIRED]

“…Nine studies used fluorescence in situ hybridization (FISH) of subtelomeric probes to detect chromosomal rearrangements [68][69][70]72,[74][75][76][77][78] and two studies used microsatellite markers. 71,73 The latter approach is able to detect uniparental disomy (inheritance of both copies of one chromosome from the same parent).…”