Trisomy 15 mosaicism and uniparental disomy (UPD) in a liveborn infant

Abstract

We describe a liveborn infant with uniparental disomy (UPD) with trisomy 15 mosaicism. Third trimester amniocentesis yielded a 46,XX/47,XX,+15 karyotype. Symmetrical growth retardation, distinct craniofacies, congenital heart disease, severe hypotonia and minor skeletal anomalies were noted. The infant died at 6 weeks of life. Peripheral lymphocyte chromosomes were “normal” 46,XX in 100 cells. Parental lymphocyte chromosomes were normal. Skin biopsy showed 47,XX,+15 in 80% of fibroblasts and results were equivalent in fibroblasts from autopsy lung tissue. Molecular analysis revealed maternal uniparental heterodisomy for chromosome 15 in the 46,XX cell line. We describe an emerging phenotype of trisomy 15 mosaicism, confirm that more than one tissue should be studied in all cases of suspected mosaicism, and suggest that UPD be considered in all such cases. © 1996 Wiley‐Liss, Inc.

Relaxation of imprinting in Prader-Willi syndrome

“…(2) only a subset of imprinted loci were expressed, instead of all loci, which would be expected if the paternal chromosome were present; (3) synchronous DNA replication was found only at SNRPN; (4) the phenotype of mosaic trisomy 15 was not apparent (Milunsky et al 1996;Buhler et al 1996); and (5) UPD and BPD cell lines present in a single individual would have required independent postzygotic errors (Cassidy et al 1992). Expression of imprinted genes is more likely to be the result of the relaxation of maternal alleles in the 15q11-q13 interval.…”

Mosaic trisomy 15 in a short girl with hemihypotrophy and mental retardation

“…In all patients reported so far mosaic trisomy 15 was diagnosed prenatally by CVS or amniocentesis or during the first weeks of life because of obvious dysmorphic signs (Milunsky et al, 1996;Olander et al, 2000;Markovic et al, 1996;Bennett et al, 1992;Gerard-Blanluet et al, 2001;Sundberg et al, 1994;Zaslav et al, 1998;Bühler et al, 1996;Fryns et al, 1993). In most cases the diagnosis lead to the interruption of the pregnancy.…”

“…In most cases the diagnosis lead to the interruption of the pregnancy. One patient died at the age of 6 weeks due to cardiorespiratory complications during viral infection (Milunsky et al, 1996). The others were still alive at the time of publication (Olander et al, 2000;Gerard-Blanluet et al, 2001;Bühler et al, 1996;Fryns et al, 1993).…”

“…All affected patients had minor facial dysmorphisms; most of them were mentally retarded and had congenital heart defects. Some of them had additional signs and symptoms characteristic of Prader-Willi syndrome due to uniparental maternal disomy (UPD) for chromosome 15 (Milunsky et al, 1996;Olander et al, 2000).…”

Uniparental Disomy and Genome Imprinting: an Overview

“…Trisomy rescue may occur in two distinct ways at the first zygotic cleavage by chromatid nondisjunction at metaphase or chromosome lag at anaphase, or at various stages thereafter by the same mechanisms, with the initial zygotic makeup preserved in one stem cell. Figure 2 illustrates how trisomy rescue may operate [8,9,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] by reduction to disomy according to two distinct mechanisms, both of which can generate mosaicism, in theory at least [38][39][40][41][42][43][44][45].…”