Recurrent 70.8Mb 4q22.2q32.3 duplication due to ovarian germinal mosaicism

Lucie Tosca (1) , Sophie Brisset (1) , François M Petit (1) , Laure Lecerf (1) , Ghislaine Rousseau (1) , Cécile Bas (1) , Mireille Laroudie (1) , Marie-Laure Maurin (1) , Sylvie Tapia (1) , Olivier Picone (1) , Sylvie Prevot (1) , Michel Goossens (1) , Philippe Labrune (1) , Gérard Tachdjian (1)

1 Unité Fonctionnelle de Cytogénétique, Service d'Histologie Embryologie Cytogénétique

A mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. Chromosomal germinal mosaicism occurs in germ cells prior to the onset of meiosis. Previously, few studies have described germinal mosaicism. In the present study we report on two siblings who carried identical pure and direct interstitial 4q22.2q32.3 duplication. Procedure investigations included complete clinical description, conventional cytogenetic analysis, fluorescence in situ hybridisation (FISH), comparative genomic hybridisation (CGH) array experiments and microsatellite study searching for parental origin of the duplication. Microarray CGH and further FISH experiments with BAC clones showed the same 70.8Mb direct duplication dup(4)(q22.2q32.3). Molecular studies of the 4q duplication were consistent with maternal origin associated with mitotic or meiotic rearrangements. This structural chromosomal aberration was associated in both cases with increased nuchal translucency, growth retardation and dysmorphy. Cardiopathy and lung malformations were only evident in the first case. These clinical manifestations are similar to those previously reported in previous studies involving pure 4q trisomy of the same region, save thumb and renal abnormalities that were not obvious in the presented cases. The amplified region included genes involved in neurologic development (NEUROG2, MAB21L2, PCDH10/18, GRIA2). The recurrent 4q duplication in these siblings is consistent with a maternal ovarian germinal mosaicism. This is the first description of germinal mosaicism for a large chromosomal duplication and highlights that genetic counselling for apparently de novo chromosome aberration should be taken with care.

Mots clés: chromosome 4; duplication; recurrence

Lucie Tosca, Sophie Brisset, François M Petit, Laure Lecerf, Ghislaine Rousseau, et al.. Recurrent 70.8Mb 4q22.2q32.3 duplication due to ovarian germinal mosaicism. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.46⟩. ⟨hal-00530216⟩