Abstract
Angelman syndrome (AS) is a rare neurogenetic imprinting disorder caused by the loss of function of UBE3A. In ~3-5% of AS patients, the disease is due to an imprinting defect (ID). These patients lack DNA methylation of the maternal SNRPN promotor so that a large SNRPN sense/UBE3A antisense transcript (SNHG14) is expressed, which silences UBE3A. In very rare cases, the ID is caused by a deletion of the AS imprinting centre (AS-IC). To search for sequence alterations, we sequenced this region in 168 patients without an AS-IC deletion, but did not detect any sequence alteration. However, the AS-IC harbours six common variants (five single nucleotide variants and one TATG insertion/deletion variant), which constitute five common haplotypes. To determine if any of these haplotypes is associated with an increased risk for an ID, we investigated 119 informative AS-ID trios with the transmission disequilibrium test, which is a family-based association test that measures the over-transmission of an allele or haplotype from heterozygous parents to affected offspring. By this we observed maternal over-transmission of haplotype H-AS3 (p = 0.0073). Interestingly, H-AS3 is the only haplotype that includes the TATG deletion allele. We conclu...Continue Reading
References
Apr 1, 1995·Nature Genetics·K BuitingB Horsthemke
Jan 25, 2003·American Journal of Human Genetics·Karin BuitingBernhard Horsthemke
Dec 3, 2003·Human Molecular Genetics·Adele MurrellWolf Reik
Apr 6, 2006·European Journal of Human Genetics : EJHG·Corinna ZogelBernhard Horsthemke
Jan 13, 2009·Genes & Development·Mita ChotaliaGavin Kelsey
Jun 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yotam KaufmanRuth Shemer
Jan 14, 2012·PLoS Genetics·Emily Y SmithJames L Resnick
Jan 8, 2013·Cell Stem Cell·Abby Sarkar, Konrad Hochedlinger
Nov 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michael W LewisJames L Resnick
Feb 4, 2016·European Journal of Human Genetics : EJHG·Jasmin BeygoKarin Buiting
Aug 31, 2016·Nature Reviews. Genetics·Walfred W C TangM Azim Surani
Sep 13, 2016·Nature Reviews. Neurology·Karin BuitingBernhard Horsthemke
Dec 3, 2016·Epigenetics : Official Journal of the DNA Methylation Society·David MonkUNKNOWN Nomenclature group of the European Network for Human Congenital Imprinting Disorders
Apr 22, 2017·Development·Vir B SinghMichael J Higgins
Sep 20, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Corey L Bretz, Joomyeong Kim
Jun 8, 2018·Epigenetics & Chromatin·Keiichiro JohHidenobu Soejima
Sep 28, 2018·Human Molecular Genetics·Michael W LewisJames L Resnick
Jan 13, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Federica Maria ValenteFlavia Cerrato
Feb 20, 2019·European Journal of Human Genetics : EJHG·Jasmin BeygoKarin Buiting
Citations
Oct 4, 2020·Scientific Reports·Serena MichelettiElisa Fazzi
Feb 21, 2021·Neurochemical Research·Guanglin ZhangJun Xing
Mar 5, 2021·Frontiers in Genetics·Aron Judd P Mendiola, Janine M LaSalle
Jun 29, 2021·Frontiers in Neurology·Altynshash JaxybayevaKymbat Jamanbekova