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Unit on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development (C.A.S., L.S.K.), National Institutes of Health, Bethesda, Maryland 20892; and Department of Laboratory Medicine and Pathology (J.A.C.), Emeritus Staff, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905
Address all correspondence and requests for reprints to: Constantine A. Stratakis, M.D., DSc, Chief, Unit on Genetics and Endocrinology, DEB, NICHD, NIH, Building 10, Room 10N262, 10 Center Drive MSC1862, Bethesda, Maryland 20892-1862. E-mail: stratakc{at}cc1.nichd.nih.gov
Abstract
Carney complex is a multiple neoplasia syndrome featuring
cardiac, endocrine, cutaneous, and neural tumors, as well as a variety
of pigmented lesions of the skin and mucosae. Carney complex is
inherited as an autosomal dominant trait and may simultaneously involve
multiple endocrine glands, as in the classic multiple endocrine
neoplasia syndromes 1 and 2. Carney complex also has some similarities
to McCuneAlbright syndrome, a sporadic condition that is also
characterized by multiple endocrine and nonendocrine tumors. Carney
complex shares skin abnormalities and some nonendocrine tumors with the
lentiginoses and certain of the hamartomatoses, particularly
Peutz-Jeghers syndrome, with which it shares mucosal lentiginosis and
an unusual gonadal tumor, large-cell calcifying Sertoli cell tumor.
Careful clinical analysis has enabled positional cloning efforts to
identify two chromosomal loci harboring potential candidate genes for
Carney complex. Most recently, at the 17q22–24 locus, the tumor
suppressor gene PRKAR1A, coding for the type 1
regulatory subunit of PKA, was found to be mutated in approximately
half of the known Carney complex kindreds. PRKAR1A acts
a classic tumor suppressor gene as demonstrated by loss of
heterozygosity at the 17q22–24 locus in tumors associated with the
complex. The second locus, at chromosome 2p16, to which most (but not
all) of the remaining kindreds map, is also involved in the molecular
pathogenesis of Carney complex tumors, as demonstrated by multiple
genetic changes at this locus, including loss of heterozygosity and
copy number gain. Despite the known genetic heterogeneity in the
disease, clinical analysis has not detected any corresponding
phenotypic differences between patients with PRKAR1A
mutations and those without. This article summarizes the clinical
manifestations of Carney complex from a worldwide collection of
affected patients and also presents revised diagnostic criteria for
Carney complex. In light of the recent identification of mutations
in the PRKAR1A gene, an estimate of penetrance and
recommendations for genetic screening are provided.
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C. A. Koch, K. Pacak, and G. P. Chrousos The Molecular Pathogenesis of Hereditary and Sporadic Adrenocortical and Adrenomedullary Tumors J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5367 - 5384. [Abstract] [Full Text] [PDF]
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F Sandrini, L S Kirschner, T Bei, C Farmakidis, J Yasufuku-Takano, K Takano, T R Prezant, S J Marx, W E Farrell, R N Clayton, et al. PRKAR1A, one of the Carney complex genes, and its locus (17q22-24) are rarely altered in pituitary tumours outside the Carney complex J. Med. Genet., December 1, 2002; 39(12): e78 - 78. [Full Text] [PDF]
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L. Groussin, E. Jullian, K. Perlemoine, A. Louvel, B. Leheup, J. P. Luton, X. Bertagna, and J. Bertherat Mutations of the PRKAR1A Gene in Cushing's Syndrome due to Sporadic Primary Pigmented Nodular Adrenocortical Disease J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4324 - 4329. [Abstract] [Full Text] [PDF]
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