The identification of a PRKACA duplication at 19p13.12 in a female with PPNAD and thyroid carcinoma after a 20-year diagnostic journey

Vollständiger Abstract

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Abstract Rare pathogenic variants affecting components of the evolutionary conserved cAMP/protein kinase A (PKA) signalling pathway are implicated in a spectrum of adrenocortical disorders. Germline inactivating PRKAR1A variants leading to constitutive PKA activation, underlie primary pigmented nodular adrenocortical disease (PPNAD) in Carney complex. More recently, several patients with PPNAD and other types of bilateral nodular adrenal disease (BNAD) have been diagnosed with rearrangements in chromosome 19 at band p13.12, resulting in copy number gains of the entire PRKACA gene. Here, we report the identification of a 19p13.12 rearrangement, resulting in a duplication of the PRKACA gene, in a 32-year-old female from whom the genetic aetiology remained unknown for 20 years. Furthermore, we provide an updated overview of patients with PRKACA germline copy number gains that have previously been reported in the literature.