Chromosome 15 uniparental disomy is not frequent in Angelman syndrome.
Genetic imprinting has been implicated in the etiology of two clinically distinct but cytogenetically indistinguishable disorders--Angelman syndrome (AS) and Prader-Willi syndrome (PWS). This hypothesis is derived from two lines of evidence. First, while the molecular extents of de novo cytogenetic deletions of chromosome 15q11q13 in AS and PWS patients are the same, the deletions originate from different parental chromosomes. In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15. The second line of evidence comes from the deletion of an abnormal parental contribution of 15q11q13 in PWS patients without a cytogenetic and molecular deletion. These patients have two maternal copies and no paternal copy of 15q11q13 (maternal uniparental disomy) instead of one copy from each parent. By qualitative hybridization with chromosome 15q11q13 specific DNA markers, we have now examined DNA samples from 10 AS patients (at least seven of which are familial cases) with no cytogenetic or molecular deletion of chromosome 15q11q13. Inheritance of one maternal copy and one paternal copy of 15q11q13 was observed in each family, suggesting that paternal uniparental disomy of 15q11q13 is not responsible for expression of the AS phenotype in these patients.
Knoll
J H
JH
Division of Genetics, Children's Hospital, Boston, MA 02115.
Glatt
K A
KA
Nicholls
R D
RD
Malcolm
S
S
Lalande
M
M
D000015:Abnormalities, Multiple / Q000235:genetics*; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D015342:DNA Probes; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D011218:Prader-Willi Syndrome / Q000235:genetics*; D013577:Syndrome
D015342:DNA Probes; D005819:Genetic Markers