RESUMO
SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.
RESUMO
In this study, ITS sequences of the nuclear ribosomal DNA were conducted for six putative species of Orinus (O. alticulmus, O. anomala, O. kokonorica, O. longiglumis, O. thoroldii and O. tibeticus) with 572 individuals from 73 populations. The results found that the six species formed two monophyletic groups: the one (O. anomala Keng ex Keng f. and L. Liou) with O. alticulmus, O. anomala and O. kokonorica, and another (O. thoroldii (Stapfex Hemsl.) Bor) with O. longiglumis, O. thoroldii and O. tibeticus. The taxonomic data from ITS sequences were not congruent with those from morphological characteristics, likely resulting from rapid speciation trigged by the uplifts of the Qinghai-Tibetan Plateau and its adjacent regions and the extensive selection pressure under the alpine environments. The ITS data suggest that the classification of the six species within the genus Orinus should be reduced to two species. We include a complete taxonomic revision of the genus and a key to distinguish the two species. Therefore, it is very necessary to make the comprehensive revision and arrangement of these taxa, strictly regulate the taxa confusion of genus and species order, and do new reports on belonging to the genus taxa.
Neste estudo, sequências ITS do DNA ribossômico nuclear foram conduzidas para seis espécies putativas de Orinus (O. alticulmus, O. anomala, O. kokonorica, O. longiglumis, O. thoroldii and O. tibeticus) com 572 indivíduos de 73 populações. Os resultados revelaram que as seis espécies formaram dois grupos monofiléticos: o primeiro (O. anomala Keng ex Keng f. and L. Liou) com O. alticulmus, O. anomala and O. kokonorica, e o segundo (O. thoroldii (Stapfex Hemsl.) Bor) com O. longiglumis, O. thoroldii and O. tibeticus. Os dados taxonômicos das sequências ITS não foram congruentes com aqueles das características morfológicas, provavelmente resultantes da rápida especiação provocada pelas elevações do Planalto do Tibete e das suas regiões adjacentes e da grande pressão de seleção nos ambientes alpinos. Os dados ITS sugerem que a classificação das seis espécies dentro do gênero Orinus deveriam ser reduzidas para duas espécies. Nós incluímos uma revisão taxonômica completa do gênero e uma chave para distinguir as duas espécies. Portanto, é absolutamente necessário fazer uma revisão abrangente e um arranjo destes táxons, regular estritamente a confusão de táxons de gêneros e ordem de espécies, e fazer novos relatórios sobre pertencer aos táxons de gêneros.