RESUMO
CONTEXT: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, usually characterized by functioning adrenal macronodules and increased cortisol production. Familial clustering of PMAH has been described, suggesting an inherited genetic cause for this condition. OBJECTIVE: The aim of the present study was to identify the gene responsible for familial PMAH. PATIENTS AND METHODS: Forty-seven individuals of a Brazilian family with PMAH were evaluated. A single-nucleotide polymorphism-based genome-wide linkage analysis followed by whole-exome sequencing were then performed in selected family members. Additionally, 29 other patients with PMAH and 125 randomly selected healthy individuals were studied to validate the genetic findings. Moreover, PMAH tissue was also analyzed through whole-exome sequencing, conventional sequencing, and microsatellite analysis. RESULTS: A heterozygous germline variant in the ARMC5 gene (p.Leu365Pro) was identified by whole-exome sequencing in a candidate genomic region (16p11.2). Subsequently, the same variant was confirmed by conventional sequencing in all 16 affected family members. The variant was predicted to be damaging by in silico methods and was not found in available online databases or in the 125 selected healthy individuals. Seven additional ARMC5 variants were subsequently identified in 5 of 21 patients with apparently sporadic PMAH and in 2 of 3 families with the disease. Further molecular analysis identified a somatic mutational event in 4 patients whose adrenal tissue was available. CONCLUSIONS: Inherited autosomal dominant mutations in the ARMC5 gene are a frequent cause of PMAH. Biallelic inactivation of ARMC5 is consistent with its role as a potential tumor suppressor gene.
Assuntos
Síndrome de Cushing/genética , Predisposição Genética para Doença , Mutação de Sentido Incorreto , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas do Domínio Armadillo , Brasil , Síndrome de Cushing/epidemiologia , Feminino , Frequência do Gene , Ligação Genética , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
Os angiomiolipomas são lesões geralmente benignas. Caracterizamsepela presença de tecido adiposo maduro, músculo liso e vasos sangüíneos com parede espessada. Os angiomiolipomas são lesões assintomáticas, porém em 10% dos casos, geralmente em tumoresmaiores, pode ocorrer sangramento intenso, acompanhado de choquehipovolêmico. Relata-se o caso de uma mulher de 33 anos, com rotura espontânea de um angiomiolipoma, tratada inicialmente por embolização da lesão, que estabilizou o quadro clínico da paciente, sendo posteriormente realizada nefrectomia parcial.
Assuntos
Humanos , Feminino , Adulto , Angiomiolipoma/cirurgia , Hemorragia , Neoplasias Renais , RupturaRESUMO
Os autores apresentam um caso de síndrome de Budd-Chiari e suas correlaçöes clínicas, radiológicas e patológicas
