Disruption of the bipartite imprinting center in a family with Angelman syndrome.
Imprinting in 15q11-q13 is controlled by a bipartite imprinting center (IC), which maps to the SNURF-SNRPN locus. Deletions of the exon 1 region impair the establishment or maintenance of the paternal imprint and can cause Prader-Willi syndrome (PWS). Deletions of a region 35 kb upstream of exon 1 impair maternal imprinting and can cause Angelman syndrome (AS). So far, in all affected sibs with an imprinting defect, an inherited IC deletion was identified. We report on two sibs with AS who do not have an IC deletion but instead have a 1-1.5 Mb inversion separating the two IC elements. The inversion is transmitted silently through the male germline but impairs maternal imprinting after transmission through the female germline. Our findings suggest that the close proximity and/or the correct orientation of the two IC elements are/is necessary for the establishment of a maternal imprint.
Buiting
K
K
Institut für Humangenetik, Universitätsklinikum Essen, 45122 Essen, Germany. karin.buiting@uni-essen.de
Barnicoat
A
A
Lich
C
C
Pembrey
M
M
Malcolm
S
S
Horsthemke
B
B
D017204:Angelman Syndrome / Q000235:genetics*; D001483:Base Sequence; D007446:Chromosome Inversion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D009679:Nuclear Family; D010375:Pedigree; D011218:Prader-Willi Syndrome / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*