Mosaic paternal uniparental (iso)disomy for chromosome 20 associated with multiple anomalies.
Uniparental disomy for a number of human chromosomes is associated with clinical abnormalities. We report a child with a complex chromosomal rearrangement involving chromosome 20 (45,XY,psu dic (20;20)(p13;p13)) and paternal uniparental isodisomy for chromosome 20 in peripheral blood and bone marrow. This patient had multiple congenital abnormalities including microtia/anotia, micrencephaly, congenital heart disease, neuronal subependymal heterotopias, and colonic agangliosis. Molecular studies on DNA from peripheral blood demonstrated paternal uniparental inheritance of chromosome 20. However, fibroblasts demonstrated a mosaic karyotype, with one cell line having 45 chromosomes, including the pseudodicentric chromosome 20 (75% of cells), and a second cell line having 46 chromosomes, including the pseudodicentric chromosome 20, and a normal chromosome 20 (trisomy 20) (25% of cells). FISH experiments using a sub-telomeric probe that maps approximately 120 kb from the 20p telomere, showed that both copies of these sequences were present on the rearranged chromosome, consistent with deletion of a very small interval. This leads us to suggest that in addition to trisomy 20 mosaicism, paternal uniparental disomy for chromosome 20 could contribute to his clinical phenotype.
Venditti
Charles P
CP
Division of Human Genetics and Molecular Biology, Department of Pediatrics, The Children's Hospital of Philadelphia, Pennsylvania , USA.
Hunt
Piper
P
Donnenfeld
Alan
A
Zackai
Elaine
E
Spinner
Nancy B
NB
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000473:pathology; D002828:Choristoma / Q000473:pathology; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000473:pathology*; D004805:Ependyma; D005192:Family Health; D006330:Heart Defects, Congenital / Q000473:pathology*; D006627:Hirschsprung Disease / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D009030:Mosaicism; D009474:Neurons; D010375:Pedigree; D024182:Uniparental Disomy