A Novel Missense PRKAR1A Variant Causes Carney Complex

Figures

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  Fig. 1.. The patient’s adrenal gland. (A) Adrenal computed tomography was performed as cortisol level was elevated in the examination, considering secondary hypertension. Adrenal computed tomography revealed multiple small nodules in both the adrenal glands (arrows). (B) Pigmented micronodules were observed throughout the cortex of the adrenal gland in the patient who underwent adrenalectomy (arrows).

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  Fig. 2.. The patient’s pedigree analysis, sequencing analysis of protein kinase A regulatory subunit 1 alpha (PRKAR1A), and the protein kinase A (PKA) activity and cyclic adenosine monophosphate (cAMP) levels in PRKAR1A mutants. (A) Family tree of the patient diagnosed with the Carney complex. The patient’s mother had acromegaly and adrenal Cushing’s syndrome and died of colon cancer. Both her uncles were treated for acromegaly. Genetic testing confirmed the same variant in all of her mother’s brothers, one sister, and four symptomatic cousins (*). Two cousins (III.3 and III.8) are asymptomatic carriers. Family members who underwent genetic testing for the variant of PRKAR1A. (B) DNA sequencing result showing a novel missense variant, NM_002734.5(PRKAR1A): c.176A>T. (C) RNA sequencing analysis showing the absence of the variant. (D) Relative PKA activity was significantly higher in both a previously known mutant (c.491_492del) and the new mutant found in the patient of this study (c.176A>T) than in the wild type (WT), and there was no significant difference in the relative PKA activity between the c.491_492del and c.176A>T mutants. (E) Relative cAMP level in both the c.491_492del and…