Prenatal detection of subtelomeric rearrangements by multi-subtelomere FISH in a cohort of fetuses with major malformations

Am J Med Genet A. 2006 Dec 15;140(24):2768-75. doi: 10.1002/ajmg.a.31472.

Abstract

Cryptic unbalanced subtelomeric rearrangements have been identified as an important contributor ( approximately 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amniocentesis
  • Chromosome Aberrations*
  • Cohort Studies
  • Congenital Abnormalities / diagnosis
  • Congenital Abnormalities / diagnostic imaging
  • Congenital Abnormalities / genetics*
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Male
  • Polymorphism, Genetic
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Telomere / genetics*
  • Ultrasonography, Prenatal