Key result
A novel PRKAR1A mutation (553delG) was identified in three family members affected by Carney complex, but absent in unaffected relatives, sporadic cardiac myxoma patients, and healthy controls.
Observational (n=121)
The identification of the 553delG mutation in PRKAR1A expands the genetic spectrum of Carney complex and suggests haploinsufficiency via nonsense-mediated mRNA decay as the disease mechanism.
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Expands PRKAR1A variant spectrum in Carney complex; leaves open screening and counseling implications pending larger validation.
Mutations of the PRKAR1A gene are an important cause of Carney complex (CC). The PRKAR1A gene encodes the type 1A regulatory subunit of cAMP-dependent protein kinase A. We have identified one mutation of PRKAR1A (553delG) in three members of the same family affected by CC. This mutation was not identified in six unaffected family members, 12 patients with sporadic cardiac myxoma and 100 non-related healthy individuals. The novel mutation (553delG) is predicted to produce a frameshift leading to a premature stop codon. RNA analysis in the index patient showed normal size transcripts in RT-PCR amplicons of several exons, but an overall tendency to lower amounts of transcripts in relation to GAPDH controls. In Western blot analyses only full-length protein was present without any evidence of truncated product. These data suggest that the mutant allele might be a null allele due to degradation of the mutant mRNA via nonsense-mediated decay.
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Vargas‐Alarcón et al. (2008) conducted an observational in Carney complex (n=121). PRKAR1A gene mutation (553delG) vs. Unaffected family members, sporadic cardiac myxoma patients, and healthy individuals was evaluated on Presence of PRKAR1A 553delG mutation. A novel PRKAR1A mutation (553delG) was identified in three family members affected by Carney complex, but absent in unaffected relatives, sporadic cardiac myxoma patients, and healthy controls.
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