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A Novel Missense PRKAR1A Variant Causes Carney Complex.

ABSTRACT: The Carney complex (CNC) is an autosomal dominant disorder characterized by endocrine and nonendocrine tumors. Loss-of-function variants of protein kinase A regulatory subunit 1 alpha (PRKAR1A) are common causes of CNC. Here, we present the case of a patient with CNC with a novel PRKAR1A missense variant. A 21-year-old woman was diagnosed with CNC secondary to acromegaly and adrenal Cushing syndrome. Genetic analysis revealed a novel missense heterozygous variant of PRKAR1A (c.176A>T). Her relatives, suspected of having CNC, also carried the same variant. RNA analysis revealed that this variant led to nonsense-mediated mRNA decay. In vitro functional analysis of the variant confirmed its role in increasing protein kinase A activity and cyclic adenosine monophosphate levels. This study broadens our understanding of the genetic spectrum of CNC. We suggest that PRKAR1A genetic testing and counseling be recommended for patients with CNC and their families.

SUBMITTER: Kim B

PROVIDER: S-EPMC9633213 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A Novel Missense PRKAR1A Variant Causes Carney Complex.

Kim Boram B Jang Han Na HN Chae Kyung Shil KS Shin Ho Seop HS Kim Yong Hwy YH Kim Su Jin SJ Seong Moon-Woo MW Kim Jung Hee JH

Endocrinology and metabolism (Seoul, Korea) 20221004 5

The Carney complex (CNC) is an autosomal dominant disorder characterized by endocrine and nonendocrine tumors. Loss-of-function variants of protein kinase A regulatory subunit 1 alpha (PRKAR1A) are common causes of CNC. Here, we present the case of a patient with CNC with a novel PRKAR1A missense variant. A 21-year-old woman was diagnosed with CNC secondary to acromegaly and adrenal Cushing syndrome. Genetic analysis revealed a novel missense heterozygous variant of PRKAR1A (c.176A>T). Her relat ...[more]

PMID: 36193716

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A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations.

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Systematic screening for PRKAR1A gene rearrangement in Carney complex: identification and functional characterization of a new in-frame deletion.

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| S-EPMC4733623 | biostudies-literature

A Titin Missense Variant Causes Atrial Fibrillation.

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| S-EPMC11643245 | biostudies-literature

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