title: Prenatal detection of subtelomeric rearrangements by multi-subtelomere FISH in a cohort of fetuses with major malformations.
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.
authors.affiliation: Laboratoire de Cytogénétique Prénatale, Service de Génétique Médicale, CHU Sainte-Justine, Montréal, Québec, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gignac
authors.forename: Karine
authors.initials: K
authors.lastname: Danis
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tihy
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lemyre
mesh_terms: D000328:Adult; D000649:Amniocentesis; D002869:Chromosome Aberrations; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D016615:Telomere / Q000235:genetics*; D016216:Ultrasonography, Prenatal