Somatic mosaicism in patients with Angelman syndrome and an imprinting defect

Hülya Nazlican, Michael Zeschnigk, Uwe Claussen, Susanne Michel, Stefan Boehringer, Gabriele Gillessen-Kaesbach, Karin Buiting*, Bernhard Horsthemke

*Korrespondierende/r Autor/-in für diese Arbeit
63 Zitate (Scopus)

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 analyst 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.

OriginalspracheEnglisch
ZeitschriftHuman Molecular Genetics
Jahrgang13
Ausgabenummer21
Seiten (von - bis)2547-2555
Seitenumfang9
ISSN0964-6906
DOIs
PublikationsstatusVeröffentlicht - 01.11.2004

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  • Querschnittsbereich: Medizinische Genetik

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