Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.

OBJECTIVE: To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. METHODS: A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome " and "FOXC2 ". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-046-01). RESULTS: Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c.361C>T (p.R121C) variant and a c.168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. CONCLUSION The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c.168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; East Asian People/genetics* ; Eyelashes/abnormalities* ; Forkhead Transcription Factors/genetics* ; Genetic Testing ; Lymphedema/genetics* ; Pedigree ; Phenotype ; Retrospective Studies

Objective To explore the effects of silencing HERC4 on the proliferation,apoptosis,and migration of cervical cancer cell line Hela and the possible molecular mechanisms.Methods Three HERC4-specific small interfering RNAs (siRNAs) were transfected into Hela cells,and HERC4 expression in the cells was examined with Western blotting.CCK-8 assay,annexin V-FITC/PI assay,and wound healing assay were used to assess the effect of HERC4 silencing on the proliferation,apoptosis and migration ability of Hela cells.The expression levels of cyclin D1 and Bcl-2 in the cells were detected using Western blotting.Results Transfection of siRNA-3 resulted in significantly decreased HERC4 protein expression (P＜0.01).HERC4 silencing by siRNA-3 markedly suppressed the proliferation and migration of Hela cells,increased the apoptosis rate (P＜0.01) and reduced the expression levels of cyclin D1 and Bcl-2 (P＜0.01).Conclusion Silencing of HERC4 efficiently inhibits the proliferation,migration,and invasion of Hela cells in vitro,and the underlying mechanisms may involve the down-regulation of cyclin D1 and Bcl-2.

Objective To explore the effects of silencing HERC4 on the proliferation,apoptosis,and migration of cervical cancer cell line Hela and the possible molecular mechanisms.Methods Three HERC4-specific small interfering RNAs (siRNAs) were transfected into Hela cells,and HERC4 expression in the cells was examined with Western blotting.CCK-8 assay,annexin V-FITC/PI assay,and wound healing assay were used to assess the effect of HERC4 silencing on the proliferation,apoptosis and migration ability of Hela cells.The expression levels of cyclin D1 and Bcl-2 in the cells were detected using Western blotting.Results Transfection of siRNA-3 resulted in significantly decreased HERC4 protein expression (P＜0.01).HERC4 silencing by siRNA-3 markedly suppressed the proliferation and migration of Hela cells,increased the apoptosis rate (P＜0.01) and reduced the expression levels of cyclin D1 and Bcl-2 (P＜0.01).Conclusion Silencing of HERC4 efficiently inhibits the proliferation,migration,and invasion of Hela cells in vitro,and the underlying mechanisms may involve the down-regulation of cyclin D1 and Bcl-2.