Trisomy 15 mosaicism owing to familial reciprocal translocation t(1;15): implication for prenatal diagnosis

Abstract

We describe a 4-year-old female child with severe global mental retardation, myoclonic epilepsy, proximal hypotonia and dysmorphisms, whose prenatal diagnosis following amniocentesis revealed a constitutional female karyotype carrying a t(1;15)(q10;p11) familial reciprocal translocation. Post-natal high-resolution karyotype, Fluorescence in situ hybridization (FISH) screening for subtelomeric rearrangements, VNTR search for UPD15 in the blood and fibroblast, and WCP1 and 15 in the mother, failed to provide an explanation for the complex clinical phenotype of the proband. Since the pachytene configuration of the translocated chromosomes defines a high probability of 3:1 segregation, an extensive workup was undertaken to look for a possibly cryptic mosaicism. Four percent of the cells with trisomy 15 was found in the peripheral blood lymphocytes examined by classical cytogenetic technique and interphase FISH analysis. The clinical features associated with cryptic trisomy 15 mosaicism and the problems concerning prenatal diagnosis and genetic counselling for carriers of translocations at high risk of 3:1 segregation are discussed.

Candidate genes for congenital diaphragmatic hernia from animal models: sequencing of FOG2 and PDGFRα reveals rare variants in diaphragmatic hernia patients

“…Trisomy 15 mosaicism has been associated with developmental delay, congenital cardiac disease, lung hypoplasia, rib anomalies, facial dysmorphism with a broad nasal bridge, an anteverted and prominent nose, a small mouth, narrow lips, ear dysplasia, FOG2 and PDGFRa variants in congenital diaphragmatic hernia SB Bleyl et al micrognathia, digital anomalies, a high or cleft palate and a short neck. 32 The physical anomalies in our patient could be related to the trisomy 15 mosaicism, the PDGFRa alteration or a combination of both. While the low level of mosaicism in this patient could represent lab artifact, it is also possible that the level of mosaicism was higher in vivo than in culture.…”

An infant with trisomy 15 mosaicism

“…Trisomy 15 accounts for 7.6% of all trisomic abortions and 1.68% of all first-trimester pregnancy losses (Prontera et al, 2006). Few cases of mosaic trisomy 15 in liveborn infants have been reported (Codwell et al, 1981;Stallard and Sommer, 1989;Kuller and Laifer, 1991;Lahdetie and Lakkala, 1992;Fryns et al, 1993;Bühler et al, 1996;Milunsky et al, 1996;Zaslav et al, 1998;Olander et al, 2000;Prontera et al, 2006).…”

Delineating the Mosaic Trisomy 15 Phenotype Using a Serendipitous Mechanism as a Clue

“…Only one case of mosaicism for trisomy 15 coexisting with a parental 1; 15 translocation has been thus far reported. In that case, the above-mentioned mechanism was demonstrated at molecular level with both the translocated chromosome and the supernumerary chromosome deriving from the mother [Prontera et al, 2006].…”

“…Trisomy 15 accounts for 7,6% of all abortions for trisomy and for 1,7% of all first-trimester pregnancy losses [Prontera et al, 2006]. Liveborns with non-mosaic trisomy 15 are extremely rare, and only 2 cases of newborns with a homogeneous 47,XX,+15 karyotype have been reported [Coldwell et al, 1981;Kuller and Laifer, 1991].…”

“…Newborns were mostly ascertained because of skeletal, craniofacial, and limb abnormalities [Coldwell et al, 1981;Stallard and Sommer, 1989;Kuller and Laifer, 1991;Fryns et al, 1993;Bühler et al, 1996;Milunsky et al, 1996;Olander et al, 2000;Gérard-Blanluet et al, 2001;KnauerFisher et al, 2004;Prontera et al, 2006;Isikay and Carman, 2013;Mc Padden et al, 2015].…”