Proximal 15q familial euchromatic variant and PWS/AS critical region duplication in the same patient: A cytogenetic pitfall

Nadège Carelle-Calmels, Françoise Girard-Lemaire, Eric Guérin, Eric Bieth, Gabrielle Rudolf, Valérie Biancalana, Hélène Pecheur, Houria Demil, Thierry Schneider, Anne de Saint-Martin, Olivier Caron, Michèle Legrain, Valérie Gaston, Elisabeth Flori

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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Résumé

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.

langue originaleAnglais
Pages (de - à)547-557
Nombre de pages11
journalEuropean Journal of Medical Genetics
Volume51
Numéro de publication6
Les DOIs
étatPublié - 1 nov. 2008
Modification externeOui

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