title: Prenatal detection of the 17p11.2 duplication in Charcot-Marie-Tooth disease type 1A: necessity of a multidisciplinary approach for heterogeneous disorders.
abstract: Charcot-Marie-Tooth (CMT) disease is a typical example of a clinically and genetically heterogeneous disorder and, in most cases, is dominantly inherited and caused by a 1.5 megabase duplication on chromosome 17p11.2 containing the PMP22 gene. This is a non-lethal disease with a wide spectrum of severity, from asymptomatism to severe motor and sensory disability. Unpredictable degree of disability is usually the reason why prenatal diagnosis is required and must be addressed. Molecular procedures such as the use of polymorphic non microsatellite STRs, allowing very fast and reliable results even when requiring a gene dosage interpretation are now available and have been recently validated in post-natal diagnosis. Our results indicate that this approach is also the best-adapted method in case of prenatal diagnosis. Nevertheless, ethical considerations raised by prenatal diagnosis in CMT and more generally in non-lethal disorders remain to be actively considered. Here, we present our experience in genetic counselling, and address the psychological issues for 7 CMT at risk pregnancies. In five cases, a CMT1A duplication was evidenced; pregnancy was terminated in four of these cases and the parents from one affected foetus decided to pursue the pregnancy.
authors.affiliation: Département de Génétique Médicale, Hôpital d'enfants de la Timone, 13385 Marseille Cedex 05, France.
authors.forename: Rafaëlle
authors.initials: R
authors.lastname: Bernard
authors.forename: Amandine
authors.initials: A
authors.lastname: Boyer
authors.forename: Philippe
authors.initials: P
authors.lastname: Nègre
authors.forename: Perrine
authors.initials: P
authors.lastname: Malzac
authors.forename: Philippe
authors.initials: P
authors.lastname: Latour
authors.forename: Antoon
authors.initials: A
authors.lastname: Vandenberghe
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000523:psychology
chemical_list: D005819:Genetic Markers