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Title: Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice
Authors: Veugelers, Mark ×
Wilkes, David
Burton, Kimberly
McDermott, Deborah A
Song, Yan
Goldstein, Marsha M
La Perle, Krista
Vaughan, Carl J
O'Hagan, Art
Bennett, Kenneth R
Meyer, Beat J
Legius, Eric
Karttunen, Mervi
Norio, Reijo
Kaariainen, Helena
Lavyne, Michael
Neau, Jean-Philippe
Richter, Gert
Kirali, Kaan
Farnsworth, Alan
Stapleton, Karen
Morelli, Peter
Takanashi, Yoshinori
Bamforth, John-Steven
Eitelberger, Franz
Noszian, Irene
Manfroi, Waldimiro
Powers, James
Mochizuki, Yoshihiko
Imai, Tsuneo
Ko, Gary T C
Driscoll, Deborah A
Goldmuntz, Elizabeth
Edelberg, Jay M
Collins, Amanda
Eccles, Diana
Irvine, Alan D
McKnight, G Stanley
Basson, Craig T #
Issue Date: Sep-2004
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:101 issue:39 pages:14222-7
Abstract: Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1alpha of protein kinase A) mutations in CNC. Mutational analyses of the PRKAR1A gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to PRKAR1A haploinsufficiency. Therefore, we studied the consequences of prkar1a haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in prkar1a(+/-) mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover, prkar1a(+/-) mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from prkar1a(+/-) mice did not exhibit prkar1a loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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