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

Authors

  • Jennifer Gignac,

    1. Laboratoire de Cytogénétique Prénatale, Service de Génétique Médicale, CHU Sainte-Justine, Montréal, Québec, Canada
    2. Centre de Recherche du CHU Sainte-Justine, CHU Sainte-Justine, Montréal, Québec, Canada
    3. Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
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  • Karine Danis,

    1. Laboratoire de Cytogénétique Prénatale, Service de Génétique Médicale, CHU Sainte-Justine, Montréal, Québec, Canada
    2. Centre de Recherche du CHU Sainte-Justine, CHU Sainte-Justine, Montréal, Québec, Canada
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  • Frédérique Tihy,

    1. Laboratoire de Cytogénétique Prénatale, Service de Génétique Médicale, CHU Sainte-Justine, Montréal, Québec, Canada
    2. Centre de Recherche du CHU Sainte-Justine, CHU Sainte-Justine, Montréal, Québec, Canada
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  • Emmanuelle Lemyre

    Corresponding author
    1. Laboratoire de Cytogénétique Prénatale, Service de Génétique Médicale, CHU Sainte-Justine, Montréal, Québec, Canada
    2. Centre de Recherche du CHU Sainte-Justine, CHU Sainte-Justine, Montréal, Québec, Canada
    3. Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
    • CHU Sainte-Justine, Service de Génétique Médicale, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, H3T 1C5 Québec, Canada.
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  • How to cite this article: Gignac J, Danis K, Tihy F, Lemyre E. 2006. Prenatal detection of subtelomeric rearrangements by multi-subtelomere FISH in a cohort of fetuses with major malformations. Am J Med Genet Part A 140A:2768–2775.

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.

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