TRISOMY FIRST, TRANSLOCATION 2ND, UNIPARENTAL DISOMY AND PARTIAL TRISOMY 3RD - A NEW MECHANISM FOR COMPLEX CHROMOSOMAL ANEUPLOIDY

A 2-year-old, short, microcephalic and developmentally retarded boy re vealed a pattern of multiple minor anomalies, hypospadias and a dyspla stic right kidney, Maternal age at delivery was 41 years. His karyotyp e showed two cell lines, one apparently normal, the other with a 1p+ c hromosome. FISH examinations showed that the segment attached to Ip wa s from chromosome 16, and molecular investigations disclosed maternal heterodisomy 16, except for the segment (16)(pter-->p13.1) for which t here was mosaicism between trisomy and uniparental disomy (UPD). Most likely, the zygote was trisomic for chromosome 16 due to a maternal me iosis I nondisjunction; a somatic rearrangement would have then occurr ed at an early postzygotic stage whereby a segment of the paternal chr omosome 16 was translocated onto Ip. Subsequently, the paternal chromo somes 16 and 16p- had been lost in the normal and the translocation ce ll line, respectively. The chromosome aberration was detected secondar y to the disclosure of maternal UPD 16 because of the demonstration of a paternal band at several loci on distal 16p. This case shows that c hromosome aberrations may be formed in a more complicated manner than primarily assumed. Hence, the phenotype might also be due to underlyin g factors such as UPD or undetected mosaicism in additon to the more o bvious implications of the chromosome rearrangement itself (e.g., part ial trisomy).