title: Proximal 15q familial euchromatic variant and PWS/AS critical region duplication in the same patient: a cytogenetic pitfall.
abstract: Cytogenetically detectable elongation of the 15q proximal region can be associated with Prader-Willi/Angelman critical region interstitial duplications or with inherited juxtacentromeric euchromatic variants. The first category has been reported in association with developmental delay and autistic disorders. These pathogenic recurrent duplications are more frequently of maternal origin and originate from unequal meiotic crossovers between chromosome 15 low-copy repeats. 15q juxtacentromeric euchromatic variants reflect polymorphic copy number variations of segments containing pseudogenes and usually segregate without apparent phenotypic consequence. Pathogenic relevant 15q11-q13 duplications are not distinguishable from the innocuous euchromatic variants with conventional cytogenetic methods. We report cytogenetic and molecular studies of a patient with hypotonia, developmental delay and epilepsy, carrying, on the same chromosome 15, both a de novo 15q11-q13 interstitial duplication and an inherited 15q juxtacentromeric amplification from maternal origin. The duplication, initially suspected by fluorescent in situ hybridization (FISH), has been confirmed by molecular studies. The 15q juxtacentromeric region amplification, which segregates in the family for at least three generations, has been confirmed by FISH using BAC probes overlapping the NF1 and GABRA5 pseudogenes. This report emphasizes the importance to distinguish proximal 15q polymorphic variants from clinically significant duplications. In any patient with inherited 15q proximal variant but unexplained developmental delay suggesting 15q11-q13 pathology, a pathogenic rearrangement has to be searched with adapted strategies, in order to detect deletions as well as duplications of this region.
authors.affiliation: Service de Cytogénétique, Fédération de Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Carelle-Calmels
authors.forename: Françoise
authors.initials: F
authors.lastname: Girard-Lemaire
authors.forename: Eric
authors.initials: E
authors.lastname: Guérin
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.forename: Valérie
authors.initials: V
authors.lastname: Biancalana
authors.forename: Hélène
authors.initials: H
authors.lastname: Pecheur
authors.forename: Houria
authors.initials: H
authors.lastname: Demil
authors.forename: Thierry
authors.initials: T
authors.lastname: Schneider
authors.forename: Anne
authors.initials: A
authors.lastname: de Saint-Martin
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
authors.forename: Michèle
authors.initials: M
authors.lastname: Legrain
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaston
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Flori
mesh_terms: D001483:Base Sequence; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002884:Chromosomes, Human, Pair 15; D017931:DNA Primers; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers