Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy.
Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). We describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor.
Section of Genetics/Dysmorphology, University of Arizona College of Medicine, Tucson 85724.
S B
SB
Cassidy
L W
LW
Lai
R P
RP
Erickson
L
L
Magnuson
E
E
Thomas
R
R
Gendron
J
J
Herrmann
D000328:Adult; D000483:Alleles; D000650:Amnion / Q000166:cytology; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15; D004262:DNA Restriction Enzymes; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008423:Maternal Age; D012150:Polymorphism, Restriction Fragment Length; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D014314:Trisomy
D004262:DNA Restriction Enzymes