Clinical phenotype and genetic analysis of a fetus with Glutaracidemia type II C / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type II C (GA II C).@*METHODS@#Clinical data of a 32-year-old pregnant woman and her fetus with GA II C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq).@*RESULTS@#At 18 weeks' gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks' gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c.1285+1G＞A and c.343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PS3_Supporting; PVS1+PM2_Supporting+PM3).@*CONCLUSION@#The c.1285+1G＞A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus. Type II C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.

Correlation of toll-like receptor 3 and tumor necrosis factor-α with idiopathic fetal growth restriction / 中华妇产科杂志

Objective To investigate the expression and the significance of toll-like receptor 3 (TLR-3)in placenta,tumor necrosis factor-α(TNF-α)in maternal and cord blood of idiopathic fetal growth restriction(IFGR),and their correlation with the pathogenesis of symmetric and asymmetric IFGR.Methods From April 2008 to April 2009,42 primiparae of singleton pregnancy and their IFGR babies,who delivered at term through cesarean section, in the Third Affiliated Hospital of Zhengzhou University were enrolled. All subjectects were divided into symmetric IFGR group (n=20) and asymmetric IFGR group (n =22). Another 42 non-IFGR pairs were randomly selected as the control group. The polink-2 plus polymerized horseradish peroxidase (HRP) immunohistochemical method and the enzyme linked immunosorbent assay (ELISA) were applied to detect TLR-3 and TNF-α levels. Results (1) The expression of TLR-3 protein were observed in all maternal placenta of the three groups. TLR-3 essentially expressed in syncytiotrophoblasts and hofbouer cells in the symmetric IFGR and control group, but expressed mostly in hofbouer cells and less in syneytiotrophoblasts in the asymmetric IFGR group. (2) The expression of TLR-3 in the syncytiotrophoblasts of the symmetric and asymmetric IFGR group was significantly lower than in the control group (111±14 and 118±11 vs. 156 ± 9, P<0. 01). The number of TLR-3 positive in Hofbourer cell in the symmetric IFGR group was lower than the control group (8. 9±2. 8 vs 17.5±2. 8, P <0. 01 ), but the number in the asymmetric IFGR group was higher (23.8±3.7) compared with the control group (P <0. 01). (3) The TNF-α levels in the maternal and cord blood of the symmetric and the asymmetric group were higher than that of the control group [maternal : (90±10) μg/L and ( 86±11 ) μg/L vs. (73±9) μg/L;cord blood: (92±12) μg/L and (96±8) μg/L vs. (79±9) μg/L;P<0.01]. (4) Neither symmetric nor the asymmetric IFGR group showed any correlations between the maternal and cord blood levels of TNF-α (P>0. 05). (5) Significant correlation was found between the TNF-α level of the cord blood and TLR-3 expression in the placenta in both the symmetric and asymmetric IFGR group(P<0. 05),but no relationship was found between the maternal blood TNF-α level and TLR-3 expression in the placenta (P>0. 05). Conclusions The variantions of TLR-3 expression in placenta and the increased expression of TNF-α in cord blood are associated with the genesis IFGR. The reduced expression of TLR-3 may related to symmetric IFGR, while the increased TLR-3 level in hofbouer cells may lead to asymmetric IFGR.