TY - JOUR
T1 - Epimutations in Prader-Willi and Angelman syndromes: A molecular study of 136 patients with an imprinting defect
AU - Buiting, Karin
AU - Groß, Stephanie
AU - Lich, Christina
AU - Gillessen-Kaesbach, Gabriele
AU - El-Maarri, Osman
AU - Horsthemke, Bernhard
N1 - Funding Information:
We are very grateful to all colleagues who sent us blood or DNA samples from the patients. We are indebted to all the patients and their families for their participation in the study. We thank Stefan Böhringer for statistical analysis and two anonymous reviewers for helpful comments. Part of this work was supported by Deutsche Forschungsgemeinschaft grant BU907/1-2.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders that are caused by the loss of function of imprinted genes in 15q11-q13. In a small group of patients, the disease is due to aberrant imprinting and gene silencing. Here, we describe the molecular analysis of 51 patients with PWS and 85 patients with AS who have such a defect. Seven patients with PWS (14%) and eight patients with AS (9%) were found to have an imprinting center (IC) deletion. Sequence analysis of 32 patients with PWS and no IC deletion and 66 patients with AS and no IC deletion did not reveal any point mutation in the critical IC elements. The presence of a faint methylated band in 27% of patients with AS and no IC deletion suggests that these patients are mosaic for an imprinting defect that occurred after fertilization. In patients with AS, the imprinting defect occurred on the chromosome that was inherited from either the maternal grandfather or grandmother; however, in all informative patients with PWS and no IC deletion, the imprinting defect occurred on the chromosome inherited from the paternal grandmother. These data suggest that this imprinting defect results from a failure to erase the maternal imprint during spermatogenesis.
AB - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders that are caused by the loss of function of imprinted genes in 15q11-q13. In a small group of patients, the disease is due to aberrant imprinting and gene silencing. Here, we describe the molecular analysis of 51 patients with PWS and 85 patients with AS who have such a defect. Seven patients with PWS (14%) and eight patients with AS (9%) were found to have an imprinting center (IC) deletion. Sequence analysis of 32 patients with PWS and no IC deletion and 66 patients with AS and no IC deletion did not reveal any point mutation in the critical IC elements. The presence of a faint methylated band in 27% of patients with AS and no IC deletion suggests that these patients are mosaic for an imprinting defect that occurred after fertilization. In patients with AS, the imprinting defect occurred on the chromosome that was inherited from either the maternal grandfather or grandmother; however, in all informative patients with PWS and no IC deletion, the imprinting defect occurred on the chromosome inherited from the paternal grandmother. These data suggest that this imprinting defect results from a failure to erase the maternal imprint during spermatogenesis.
UR - http://www.scopus.com/inward/record.url?scp=0037371674&partnerID=8YFLogxK
U2 - 10.1086/367926
DO - 10.1086/367926
M3 - Journal articles
C2 - 12545427
AN - SCOPUS:0037371674
SN - 0002-9297
VL - 72
SP - 571
EP - 577
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -
