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

Abstract

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 before the onset of meiosis. Previously, few studies have described germinal mosaicism. In this 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 hybridization (FISH), comparative genomic hybridization (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 70.8 Mb 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, except for thumb and renal abnormalities that were not obvious in the presented cases. The amplified region included genes involved in neurological development (NEUROG2, MAB21L2, PCDH10/18 and 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 undertaken with care.

Molecular characterization of distal 4q duplication in two patients using oligonucleotide array‐based comparative genomic hybridization (oaCGH) analysis

“…Pure/direct duplications of chromosome 4q have been reported in over 30 patients [Rinaldi et al, ; Elghezal et al, ; Lin et al, ; Egritas et al, ; Tosca et al, ] with the most frequently occurring breakpoint between 4q21–q28 [Rinaldi et al, ; Elghezal et al, ; Lin et al, ; Tosca et al, ]. Breakpoints between 4q12–q13 [Zollino et al, ; Shashi et al, ] and 4q31–q32 [Priest et al, ; Goodman et al, ; Maltby et al, ], on the other hand, are relatively rare.…”

Array comparative genomic hybridization analysis of small supernumerary marker chromosomes in human infertility

“…Genomic imbalances of peripheral lymphocytes were analysed by array CGH using 105k and 180k oligonucleotide arrays (Human Genome CGH Microarray 105A and Human G3 CGH Microarray 4 • 180K; Agilent Technologies, Massy, France). All array hybridizations were performed according to the manufacturer's recommended protocols and as previously described (Tosca et al, 2010). Briefly, 0.5-1 lg of genomic DNA was digested with AluI (5 units) and RsaI (5 units) for 2 h at 37°C and fluorescently labelled with a Genomic DNA PLUS labelling kit (Agilent Technologies).…”

Somatic and germ‐line mosaicism of deletion 15q11.2–q13 in a mother of dyzigotic twins with Angelman syndrome

“…Germ line mosaicism has been postulated as a possible mechanism to explain the recurrence of various genetic diseases [Zlotogora, ; Gajecka et al, ; Tosca et al, ; Pilozzi‐Edmonds et al, ; Shanske et al, ; Slavin et al, ; Steinbusch et al, ]. AS deletion due to the presence of maternal germ line mosaicism, has only been described in two families.…”