RESUMO
During Jan. 2016-Dec. 2019, nine Chinese patients from eight unrelated families were diagnosed with neonatal-onset UCDs by targeted panel sequencing or whole-exome sequencing (WES). Their clinical manifestations, biochemical features, 180-day-age outcomes, and molecular genetic characteristics were reviewed retrospectively. NGS-based tests revealed 7 patients diagnosed with ornithine transcarbamylase deficiency (OTCD) and 2 with carbamoylphosphate synthetase I deficiency (CPS1D). The spectrum of the clinical presentation of nine affected individuals progressed from unspecific symptoms like poor feeding to somnolence, coma, and death. All patients presented with an acute hyperammonemia. The most robust metabolic pattern in OTCD was hyperglutaminemic hyperammonemia with high concentration of urine orotic acid, and it was reported in six patients. Of ten variants found on the OTC gene and CPS1 gene, 3 were novel: (c.176T>C (p.L59P)) in the OTC gene, c.2938G>A (p.G980S) and c.3734T>A (p.L1245H) in the CPS1 gene. There was a high mortality rate of 77.78% (7/9) for all the defects combined. An OTC-deficient male and a CPS1-deficient female survived from episodes of hyperammonemia. Although prompt recognition of UCD and the use of alternative pathway therapy in addition to provision of appropriate nutrition and dialysis improved survival, the overall outcomes for the neonatal-onset type are poor in China.
Assuntos
Carbamoil-Fosfato Sintase (Amônia)/genética , Hiperamonemia/genética , Ornitina Carbamoiltransferase/genética , Distúrbios Congênitos do Ciclo da Ureia/genética , Idade de Início , China , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hiperamonemia/complicações , Hiperamonemia/metabolismo , Hiperamonemia/patologia , Recém-Nascido , Masculino , Metabolômica/métodos , Mutação/genética , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Doença da Deficiência de Ornitina Carbomoiltransferase/metabolismo , Doença da Deficiência de Ornitina Carbomoiltransferase/patologia , Distúrbios Congênitos do Ciclo da Ureia/complicações , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Distúrbios Congênitos do Ciclo da Ureia/patologia , Sequenciamento do ExomaRESUMO
OBJECTIVE: To explore the function and mechanism of long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in bronchopulmonary dysplasia. METHODS: Alveolar epithelial cell line BEAS-2B was used as the cell model. The role of MALAT1 and microRNA miR-129-5p in regulating cellular viability and migration were examined by using the CCK-8 and Transwell assays, respectively, in vitro. The luciferase reporter assay and real-time (RT)-PCR were performed to confirm that miR-129-5p was a target of MALAT1. ELISA was conducted to validate MALAT1 and show that miR-129-5p regulated the gene encoding high-mobility group protein 1 (HMGB1). RESULTS: Overexpression of MALAT1 significantly promoted cellular viability, whereas miR-129-5p had the opposite effect. miR-129-5p was shown to be a target of MALAT1, and HMGB1 could be upregulated by MALAT1 overexpression or miR-129-5p inhibition. CONCLUSION: MALAT1 reduced the expression of miR-129-5p, promoting the viability of cells and blocking the development of bronchopulmonary dysplasia. In addition, MALAT1 increased the expression of HMGB1, which contributed to inflammation as the disease progressed.
