Title: A new approach to imprinting mutation detection in GNAS by Sequenom EpiTYPER system
Authors: Izzi, Benedetta ×
Decallonne, Brigitte
Devriendt, Koenraad
Bouillon, Roger
Vanderschueren, Dirk
Levtchenko, Elena
de Zegher, Francis
Van den Bruel, Annick
Lambrechts, Diether
Van Geet, Christel
Freson, Kathleen #
Issue Date: Dec-2010
Publisher: Elsevier Scientific Pub. Co.
Series Title: Clinica Chimica Acta vol:411 issue:23-24 pages:2033-2039
Abstract: BACKGROUND: Pseudohypoparathyroidism type Ib (PHPIb) results from abnormal imprinting of GNAS. Familial and sporadic forms of PHPIb have distinct GNAS imprinting patterns: familial PHPIb patients have an exon A/B-only imprinting defect and an intragenic STX16 deletion, whereas sporadic PHPIb cases have abnormal imprinting of the three differentially methylated regions (DMRs) in GNAS without the STX16 deletion. Overall GNAS methylation defects have recently been detected in some PHPIa patients. METHODS: This study describes the first quantitative methylation analysis of multiple CpG sites for three different GNAS DMRs using the Sequenom EpiTYPER in 35 controls, 12 PHPIb patients, 2 PHPIa patients and 2 patients without parathormone (PTH) resistance but having only hypocalcemia and hyperphosphatemia. RESULTS: All patients have GNAS methylation defects typically with NESP hypermethylation versus XL and exon A/B hypomethylation while the imprinting of SNURF/SNRPN was normal. PHPIa patients showed an abnormal methylation in the three DMRs of GNAS. For the first time, a marked abnormal GNAS methylation was also found in 2 patients without PTH resistance but having hypocalcemia and hyperphosphatemia. CONCLUSIONS: The Sequenom EpiTYPER proves to be very sensitive in detecting DNA methylation changes. Our analysis also suggests that GNAS imprinting defects might be more frequent and diverse than previously thought.
ISSN: 0009-8981
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Section Child - Miscellaneous (-)
Section Newborn (-)
Clinical and Experimental Endocrinology
Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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