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Keywords:

  • fetus;
  • congenital malformations;
  • FISH;
  • subtelomeric rearrangements

Abstract

Cryptic unbalanced subtelomeric rearrangements have been identified as an important contributor (∼6%) to the etiology of mental retardation and dysmorphism. Our objective was to study the role of these rearrangements in the development of fetal malformations. Multi-subtelomere FISH was performed on cells from 48 fetuses with major malformations diagnosed by prenatal ultrasound with a normal karyotype at a minimal 400 band resolution. We developed a method of performing multi-subtelomere FISH on a single slide of amniocyte metaphase spreads. We identified five subtelomeric abnormalities: two derivative chromosomes inherited from a parent carrying a balanced translocation, two known polymorphisms, and one novel familial variant. These results show a similar frequency (4%) of clinically significant subtelomeric rearrangements to that found in children with multiple malformations. This study adds to a growing number of reports of cryptic subtelomeric rearrangements associated with congenital malformations and highlights the relevance and technical feasibility of multi-subtelomere FISH screening of prenatal samples. © 2006 Wiley-Liss, Inc.