Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-09

AUTHORS

Lawrence S. Kirschner, J. Aidan Carney, Svetlana D. Pack, Susan E. Taymans, Christoforos Giatzakis, Yee Sook Cho, Yoon S. Cho-Chung, Constantine A. Stratakis

ABSTRACT

Carney complex (CNC) is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and psammomatous melanotic schwannomas1,2,3,4,5. CNC is inherited as an autosomal dominant trait and the genes responsible have been mapped to 2p16 and 17q22–24 (refs 6, 7). Because of its similarities to the McCune-Albright syndrome5,8 and other features, such as paradoxical responses to endocrine signals9, genes implicated in cyclic nucleotide-dependent signalling have been considered candidates for causing CNC (ref. 10). In CNC families mapping to 17q, we detected loss of heterozygosity (LOH) in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory subunit 1-α (RIα), including a polymorphic site within its 5′ region. We subsequently identified three unrelated kindreds with an identical mutation in the coding region of PRKAR1A. Analysis of additional cases revealed the same mutation in a sporadic case of CNC, and different mutations in three other families, including one with isolated inherited cardiac myxomas. Analysis of PKA activity in CNC tumours demonstrated a decreased basal activity, but an increase in cAMP-stimulated activity compared with non-CNC tumours. We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease. More... »

PAGES

89-92

Journal

TITLE

Nature Genetics

ISSUE

1

VOLUME

26

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/79238

DOI

http://dx.doi.org/10.1038/79238

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034260511

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10973256


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60 cAMP-stimulated activity
61 candidates
62 cardiac myxoma
63 cases
64 complexes
65 cyclic nucleotide-dependent signaling
66 decreased basal activity
67 different mutations
68 disease
69 dominant trait
70 family
71 features
72 genes
73 germline mutations
74 heterozygosity
75 identical mutations
76 increase
77 kinase
78 kindreds
79 loss
80 loss of heterozygosity
81 multiple neoplasia syndrome
82 mutations
83 myxoma
84 neoplasia syndrome
85 paradoxical response
86 patients
87 phenotype
88 pigmentation
89 polymorphic sites
90 protein
91 protein kinase
92 region
93 regulatory subunit
94 regulatory subunit 1
95 response
96 same mutation
97 signaling
98 similarity
99 sites
100 skin pigmentation
101 sporadic cases
102 spotty skin pigmentation
103 subset
104 subset of patients
105 subunit 1
106 subunits
107 syndrome
108 traits
109 tumor suppressor gene
110 tumors
111 type I
112 unrelated kindreds
113 vicinity
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