Cryptic telomeric rearrangements in individuals with idiopathic mental retardation

Joyce, Christine Angela (2000) Cryptic telomeric rearrangements in individuals with idiopathic mental retardation. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Two populations of patients with unexplained developmental delay (unselected and selected), and a population 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 study population, although a semi-cryptic unbalanced telomeric translocation was identified in one selected patient by high resolution G-band analysis. A further eighteen cytogenetically detected subtle terminal rearrangements were characterised using multi-telomere FISH. Nine of these had previously been reported as normal. These results raise the possibility that cryptic telomeric rearrangements reported by other groups may also be visible with the aid of high resolution analysis.

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. A possible explanation for these unexpected findings in apparently phenotypically normal individuals is that the particular genetic imbalances in these two cases involve regions of the genome with few functional genes. These abnormalities indicate the existance of a subset of non-pathogenic, telomeric imbalances. Hence our data have important implications when defining the significance of cryptic telomeric rearrangements detected during screening programmes.

In addition, a site of cross hybridization for the 11p telomere-specific probe was identified at the telomeric region 17p. This result is indicative of sequence homology and suggests a mechanism for the origin of a familial 11p;17p translocation.

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