1. A multicenter experience on the prevalence of ARMC5 mutations in patients with primary bilateral macronodular adrenal hyperplasia: from genetic characterization to clinical phenotype
- Author
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Beatrice Rubin, Elisa Taschin, Franco Grimaldi, Carla Scaroni, Daniela Regazzo, F. Pecori Giraldi, Marco Boscaro, Nora Albiger, Alfonso Massimiliano Ferrara, Antonio Stigliano, Silvia Rizzati, Giorgio Arnaldi, E. De Menis, Maurizio Iacobone, Filippo Ceccato, Gianluca Occhi, and Lidia Cerquetti
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Primary bilateral macronodular adrenal hyperplasia ,Genotype to phenotype correlation ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,medicine.disease_cause ,ARMC5 ,Gastroenterology ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Germline mutation ,Internal medicine ,Adrenal Glands ,Genotype ,medicine ,Humans ,Family history ,Germ-Line Mutation ,Aged ,Cushing’s syndrome ,Armadillo Domain Proteins ,Mutation ,Adrenal Hyperplasia, Congenital ,business.industry ,Tumor Suppressor Proteins ,Middle Aged ,Hyperplasia ,medicine.disease ,Phenotype ,Pedigree ,Diabetes and Metabolism ,030220 oncology & carcinogenesis ,Macronodular Adrenal Hyperplasia ,Female ,business - Abstract
ARMC5 mutations have recently been identified as a common genetic cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). We aimed to assess the prevalence of ARMC5 germline mutations and correlate genotype with phenotype in a large cohort of PBMAH patients. A multicenter study was performed, collecting patients from different endocrinology units in Italy. Seventy-one PBMAH patients were screened for small mutations and large rearrangements in the ARMC5 gene: 53 were cortisol-secreting (two with a family history of adrenal hyperplasia) and 18 were non-secreting cases of PBMAH. Non-mutated and mutated patients’ clinical phenotypes were compared and related to the type of mutation. A likely causative germline ARMC5 mutation was only identified in cortisol-secreting PBMAH patients (one with a family history of adrenal hyperplasia and ten apparently sporadic cases). Screening in eight first-degree relatives of three index cases revealed four carriers of an ARMC5 mutation. Evidence of a second hit at somatic level was identified in five nodules. Mutated patients had higher cortisol levels (p = 0.062), and more severe hypertension and diabetes (p
- Published
- 2016
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