Subtelomeric Disorders Molecular Basis of Disease

Genetic imbalance caused by a chromosome abnormality frequently results in some form of developmental delay and one or more of the following: abnormal growth, dysmor-phic facial features, and congenital abnormalities. Duplications or deletions of very small chromosomal segments are often difficult or impossible to detect by routine or highresolution chromosome analysis. Though small relative to larger and thus more readily visible rearrangements, these imbalances nonetheless frequently result in an abnormal phenotype due to the resulting imbalance of multiple genes within the affected segment(s).

The subtelomeric region of each chromosome arm is located between the telomere, the functional chromosome cap, and more proximal chromosome-specific sequences.30 Subtelomeric regions and their adjoining chromosome-specific areas are of particular clinical interest for several reasons. They are particularly gene-dense regions, and shared homology within these segments may facilitate relatively frequent recombination events that may result in loss or gain of genetic material.31 This suggests that genetic imbalances in these regions may have considerable clinical consequences. Additionally, the majority of all chromosome abnormalities involve imbalance for, or movement of, a segment that contains a subtelomeric locus. Thus, testing panels have been designed to assess the genomic copy number of arm-specific loci within or near the subtelom-eric regions of each chromosome for identification of imbalances that are not readily detected by standard chromosome analysis methods.

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