OBJECTIVE: To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles. METHODS: The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4). CONCLUSION The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.
Female ; Fetus ; Genomics ; Humans ; Mutation ; Olivopontocerebellar Atrophies ; Pregnancy ; Whole Exome Sequencing

Objective:To analyze and summarize the clinical efficacy and safety of lymphocyte apheresis combined with plasma exchange in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage.Methods:A observational study was conducted. A total of 69 hepatitis B virus-related liver failure at the ascending stage patients who were hospitalized at Affiliated Guangzhou Eighth People's Hospital of Guangzhou Medical University from January 2016 to December 2020 were enrolled in this study. The patients were grouped according to their condition and wishes, including 38 patients treated with conservative medical treatment (control group) and 31 patients treated with lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment (study group). Clinical data were compared between the two groups 1-4 weeks after treatment, including dynamic changes of total bilirubin (TBil), international normalized ratio (INR), alanine aminotransferase (ALT), model for end-stage liver disease (MELD) score, and the rate of clinical improvement at 4 weeks after treatment. In addition, the adverse effects and dynamic changes of white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), and hemoglobin (Hb) within 4 weeks after treatment were compared between the two groups.Results:Both groups showed significant improvement in clinical parameters after 1-4 weeks of initiation of therapy. The improvement of TBil, INR and MELD score at 1-4 weeks after treatment were significantly better in the treatment group than those in the control group [TBil (μmol/L): 248 (117, 335) vs. 398 (328, 464) at 1 week, 173 (116, 278) vs. 326 (184, 476) at 2 weeks, 107 (84, 235) vs. 355 (129, 467) at 3 weeks, 70 (61, 172) vs. 290 (82, 534) at 4 weeks; INR: 1.72±0.70 vs. 2.13±0.69 at 1 week, 1.67±0.61 vs. 2.28±1.35 at 2 weeks, 1.65±0.75 vs. 2.15±0.92 at 3 weeks, 1.61±0.93 vs. 2.19±1.17 at 4 weeks; MELD score: 18.35±5.32 vs. 23.38±4.56 at 1 week, 16.47±5.16 vs. 23.71±7.94 at 2 weeks, 16.30±5.75 vs. 22.64±6.99 at 3 weeks, 14.63±6.76 vs. 20.97±8.19 at 4 weeks], with significant differences (all P < 0.05). In addition, ALT levels at 1 week and 2 weeks after treatment in the study group were significantly lower than those in the control group [U/L: 128 (93, 206) vs. 240 (167, 436) at 1 week, 64 (42, 110) vs. 85 (69, 143) at 2 weeks, both P < 0.05]. The rate of clinical improvement at 4 weeks after treatment in the study group was 54.84% (17/31), which was significantly higher than that in the control group [28.95% (11/38)], with statistically significant difference ( P < 0.05). There was no significant difference in the rate of new infection between the study group and the control group [22.58% (7/31) vs. 34.21% (13/38), P > 0.05]. Additionally, expect that the PLT level at 1 week after treatment in the study group was significantly lower than that in the control group (×10 9/L: 101±42 vs. 128±59, P < 0.01), there was no significant difference in WBC, LYM or Hb at different time points after treatment between the two groups. Conclusion:Clinical efficacy of lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage is superior to conservative medical treatment alone, which can improve clinical improvement rate and recovery rate of liver function with high safety.

MicroRNA (miRNA) is a non-coding small molecule RNA, which is involved in the occu-rrence and development of tumor as an oncogene or tumor suppressor gene. The abnormal expression of many kinds of miRNAs in hepatocellular carcinoma (HCC) can directly or indirectly act on PI3K, Akt, mTOR, IGF-1R, TGF-β and other signal molecules in mTOR signal pathway, they are crucial in the appreciation, invasion and metastasis of HCC cells.