RT Journal Article
T1 A PRKAR1A Mutation Associated with Primary Pigmented Nodular Adrenocortical Disease in 12 Kindreds
A1 Groussin, Lionel
A1 Horvath, Anelia
A1 Jullian, Eric
A1 Boikos, Sosipatros
A1 Rene-Corail, Fernande
A1 Lefebvre, Herve
A1 Cephise-Velayoudom, Fritz-Line
A1 Vantyghem, Marie-Cristine
A1 Chanson, Philippe
A1 Conte-Devolx, Bernard
A1 Lucas, Miguel
A1 Gentil, Alfonso
A1 Malchoff, Carl D
A1 Tissier, Frédérique
A1 Carney, J Aidan
A1 Bertagna, Xavier
A1 Stratakis, Constantine A
A1 Bertherat, Jérôme
K1 mutation
K1 disease
K1 primary pigmented nodular adrenocortical
AB CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation.OBJECTIVE:The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect.DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. PATIENTS: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD.RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers.CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.
PB Endocrine Society
YR 2006
FD 2006-05
LK http://hdl.handle.net/10668/388
UL http://hdl.handle.net/10668/388
LA en
NO Groussin L, Horvath A, Jullian E, Boikos S, Rene-Corail F, Lefebvre H, et al. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab. 2006 May;91(5):1943-9.
DS RISalud
RD Apr 11, 2025