Abstract
Five percent of patients with unexplained mental retardation have been attributed to cryptic unbalanced subtelomeric rearrangements. Half of these affected individuals have inherited the rearrangement from a parent who is a carrier for a balanced translocation. However, the frequency of carriers for cryptic balanced translocations is unknown. To determine this frequency, 565 phenotypically normal unrelated individuals were examined for balanced subtelomeric rearrangements using Fluorescent In Situ hybridization (FISH) probes for all subtelomere regions. While no balanced subtelomeric rearrangements were identified, three females in this study were determined to be mosaic for the X chromosome. Mosaicism for XXX cell lines were observed in the lymphocyte cultures of 3 in 379 women (0.8%), which is a higher frequency than the 1 in 1000 (0.1%) reported for sex chromosome aneuploidies. Our findings suggest that numerical abnormalities of the X chromosome are more common in females than previously reported. Based on a review of the literature, the incidence of cryptic translocation carriers is estimated to be approximately 1/8,000, more than ten-fold higher than the frequency of visible reciprocal translocations.
Highlights
Subtelomeres are the most distal sequences of non-repetitive DNA on the chromosome, and have the highest density of genes in the genome [1]
Among the specimens that were analyzed with subtelomeric Fluorescent In Situ hybridization (FISH) probe sets containing Xp/Yp and Xq/Yq, mosaicism for X chromosome aneuploidy was identified in 3 of 379 women (0.8%)
Subtelomeric Rearrangements No balanced cryptic translocations were found among the 565 subjects who were screened by subtelomere FISH
Summary
Subtelomeres are the most distal sequences of non-repetitive DNA on the chromosome, and have the highest density of genes in the genome [1]. Any rearrangement or deletion in these gene-rich regions could have severe phenotypic consequences. Numerous studies have shown that 0.5 to 10.7% (variation due to study selection criteria) of patients with unexplained mental retardation (MR) have an unbalanced cryptic subtelomeric rearrangement or deletion [2,3,4,5,6,7,8,9,10,11]. Parents, who are carriers of balanced translocations, are at risk for having children with unbalanced gene complements. Fifty percent of the gametes produced by a balanced translocation carrier will have segmental aneuploidy, which can result in a child with an unbalanced rearrangement. The most likely way to identify a balanced carrier is through a child who has been identified with an unbalanced rearrangement
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