Absence of PRKAR1A loss of heterozygosity in laser-captured microdissected pigmented nodular adrenocortical tissue from a patient with Carney complex caused by the novel nonsense mutation p.Y21X

Almeida, Madson Q.; Brito, Luciana Pinto; Domenice, Sorahia; Costa, Maria da Piedade Resende da; Pinto, Emília M.; Osório, Cynthia A. Toledo; Latrônico, Ana Claudia; Mendonca, Berenice B.; Fragoso, Maria Candida B. V.

doi:10.1590/s0004-27302008000800009

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…The tumor specimen might not obtain the corresponding tissue and was contaminated by the surrounding tissue. In case of somatic events, laser-captured micro-dissected cells can be used (36), and blood tissue can also be tested for genetic mutations to identify germline or somatic mutations.…”

Section: Discussionmentioning

confidence: 99%

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review

Sun,

Ding,

et al. 2024

Front. Endocrinol.

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AimsPrimary pigmented nodular adrenocortical disease (PPNAD), as a rare kind of Cushing’s syndrome, is frequently misdiagnosed. To get a better understanding of the disease, we analyzed the clinical characteristics and pathogenic variants of PPNAD.MethodsDatabases were searched, and the pathogenic variants and clinical manifestations of patients were summarized from the relevant articles.ResultsA total of 210 patients in 86 articles were enrolled with a median age of 22 and a female-to-male ratio of 2:1. Sixty-six (31.43%) patients were combined with Carney complex (CNC) and 94.29% were combined with osteoporosis/osteopenia. Among 151 patients who underwent genetic testing, 87.42% (132/151) had pathogenic variants. Six gene mutations (PRKAR1A, PDE11A, PRKACA, CTNNB1, PDE8B, and ARMC5) were detected in the patients. The most common mutation was PKAR1A, accounting for 79.47% (120/151). There was a significant correlation between PRKAR1A pathogenic variant and spotty skin pigmentation in CNC concurrent with PPNAD (p < 0.05). Among pregnant patients with PPNAD, those without surgical treatment and with bilateral adrenalectomy suffered from a high-risk perinatal period. However, patients with unilateral adrenalectomy presented a safe perinatal period.ConclusionsFor young patients with Cushing’s syndrome, especially female patients with spotty skin pigmentation and osteoporosis/osteopenia, PPNAD should be considered. Unilateral adrenal resection may be considered as an option for women with fertility needs. In view of the difficulty of PPNAD diagnosis, genetic testing before surgery might be a reasonable option. Patients with PPNAD with spotty skin pigmentation should consider the PRKAR1A pathogenic variant and pay attention to CNC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023416988.

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Section: Discussionmentioning

confidence: 99%

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review

Sun,

Ding,

et al. 2024

Front. Endocrinol.

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“…Tumour-suppressor genes generally act in a recessive way, requiring loss of both copies to induce tumorigenesis (15); it has been proposed that tumorigenesis in CNC may be caused by second hit in different tissues (16).Unfortunately, it was not possible for us to examine surgical tissues for assessing the second hit, but at least adrenocortical tumorigenesis in CNC seems to occur apart from the second hit (15) although more studies are needed.…”

Section: Discussionmentioning

confidence: 99%

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma

Ghazi¹,

Mandegar²,

Abazari³

et al. 2021

Archives of Endocrinology and Metabolism

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Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

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Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update

et al. 2010

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PRKAR1A encodes the regulatory subunit type 1-alpha (RIa) of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA). Inactivating PRKAR1A mutations are known to be responsible for the multiple neoplasia and lentiginosis syndrome Carney complex (CNC). To date, at least 117 pathogenic variants in PRKAR1A have been identified (online database: http://prkar1a.nichd.nih.gov). The majority are subject to nonsense mediated mRNA decay (NMD), leading to RIa haploinsufficiency and, as a result, activated cAMP signaling. Recently, it became apparent that CNC may be caused not only by RIa haploinsufficiency, but also by the expression of altered RIa protein, as proven by analysis of expressed mutations in the gene, consisting of aminoacid substitutions and in-frame genetic alterations. In addition, a new subgroup of mutations that potentially escape NMD and result in CNC through altered (rather than missing) protein has been analyzed-these are frame-shifts in the 3 0 end of the coding sequence that shift the stop codon downstream of the normal one. The mutation detection rate in CNC patients is recently estimated at above 60%; PRKAR1A mutation-negative CNC patients are characterized by significant phenotypic heterogeneity. In this report, we present a comprehensive analysis of all presently known PRKAR1A sequence variations and discuss their molecular context and clinical phenotype. Hum Mutat 31:369-379,

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Absence of PRKAR1A loss of heterozygosity in laser-captured microdissected pigmented nodular adrenocortical tissue from a patient with Carney complex caused by the novel nonsense mutation p.Y21X

Cited by 3 publications

References 20 publications

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma

Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update

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