Somatic mosaicism in patients with Angelman syndrome and an imprinting defect

Human Molecular Genetics
Hülya NazlicanBernhard Horsthemke

Abstract

Angelman syndrome is a neurogenetic disorder caused by the loss of function of the imprinted UBE3A gene in 15q11-q13. In a small group of patients, the disease is due to an imprinting defect (ID) that silences the maternal UBE3A allele. The presence of a faint maternal band detected by methylation-specific PCR analysis of the SNURF-SNRPN locus in approximately one-third of patients who have an ID but no imprinting center deletion suggested that these patients are mosaics of ID cells and normal cells. In two patients studied, somatic mosaicism was proven by molecular and cellular cloning, respectively. X inactivation studies of cloned fibroblasts from one patient suggest that ID occurred before the blastocyst stage. To quantify the degree of mosaicism, we developed a novel quantitative methylation assay based on real-time PCR. In 24 patients tested, the percentage of normal cells ranged from <1% to 40%. Regression analysis suggests that patients with a higher percentage of normally methylated cells tend to have milder clinical symptoms than patients with a lower percentage. In conclusion, we suggest that the role of mosaic imprinting defects in mental retardation is underestimated.

References

Jul 12, 1996·American Journal of Medical Genetics·L Carrel, H F Willard
Jul 1, 1997·American Journal of Human Genetics·J BürgerA Reis
Mar 29, 2000·Nucleic Acids Research·C A EadsP W Laird
Aug 11, 2001·Science·W ReikJ Walter
Dec 19, 2001·Journal of Medical Genetics·A C LossieD J Driscoll
Jan 25, 2003·American Journal of Human Genetics·Karin BuitingBernhard Horsthemke
Aug 6, 2003·Cytogenetic and Genome Research·M Monk
Oct 3, 2003·European Journal of Human Genetics : EJHG·Bernhard HorsthemkeHelga Weirich
Jan 31, 2004·Science·Winifred MakNeil Brockdorff
Mar 12, 2004·Human Genetics·Maren RunteKarin Buiting

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Citations

Jul 26, 2005·Human Genetics·Roberto CicconeElena Rossi
May 21, 2009·European Journal of Human Genetics : EJHG·Griet Van Buggenhout, Jean-Pierre Fryns
May 19, 2011·European Journal of Human Genetics : EJHG·Jennifer BoyleJ Ross Hawkins
Apr 6, 2006·European Journal of Human Genetics : EJHG·Corinna ZogelBernhard Horsthemke
May 7, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Charles A WilliamsAditi I Dagli
Apr 1, 2006·Cytogenetic and Genome Research·B Horsthemke, K Buiting
May 13, 2010·BMC Medical Genetics·Simon C RamsdenKarin Buiting
Dec 1, 2009·Epigenomics·Derek Hk Lim, Eamonn R Maher
Apr 20, 2010·Mutation Research·Robert P Erickson
Nov 23, 2007·American Journal of Medical Genetics. Part a·Meredith WilsonElizabeth Algar
Oct 13, 2006·American Journal of Medical Genetics. Part a·Amy Lawson-YuenVirginia Kimonis
Feb 14, 2006·American Journal of Medical Genetics. Part a·Charles A WilliamsJoseph Wagstaff
Nov 3, 2007·American Journal of Medical Genetics. Part a·Anne RonanTracy Dudding
Jul 16, 2008·American Journal of Medical Genetics. Part a·Bernhard Horsthemke, Joseph Wagstaff
Aug 31, 2010·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Bernhard Horsthemke
Aug 31, 2010·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Karin Buiting
Oct 28, 2010·American Journal of Medical Genetics. Part a·Ying Fai NgaiWilliam T Gibson
Apr 28, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Eduardo Fernández-RebolloHarald Jüppner
Dec 7, 2013·American Journal of Medical Genetics. Part a·Javier SánchezSalud Borrego
Nov 11, 2006·European Journal of Medical Genetics·Cristina CamprubíMiriam Guitart
Apr 23, 2015·American Journal of Medical Genetics. Part a·Laura C FairbrotherCharles Williams
Nov 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michael W LewisJames L Resnick
Sep 13, 2016·Nature Reviews. Neurology·Karin BuitingBernhard Horsthemke
Feb 18, 2017·American Journal of Medical Genetics. Part a·Anna Le FevreTracy Dudding-Byth
Sep 28, 2018·Human Molecular Genetics·Michael W LewisJames L Resnick
Dec 4, 2004·European Journal of Human Genetics : EJHG·Eva WeyAlessandra Baumer
Aug 8, 2018·Journal of Neurodevelopmental Disorders·Emma K BakerLesley Bretherton
Aug 11, 2019·Molecular Genetics & Genomic Medicine·Robert P CarsonJessica Duis
Sep 7, 2019·Autism Research : Official Journal of the International Society for Autism Research·Mark J Zylka
Apr 1, 2020·Genes·Flavia CerratoAndrea Riccio
Apr 27, 2018·Anesthesiology and Pain Medicine·Mary Ellen WarnerToby N Weingarten
Jan 17, 2019·Nature Reviews. Genetics·David MonkAndrea Riccio
Jun 27, 2019·European Journal of Human Genetics : EJHG·Jasmin BeygoDeniz Kanber
Feb 17, 2019·International Journal of Molecular Sciences·Thomas Liehr

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Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.