A novel missense mutation of CRYBA1 in a northern Chinese family with inherited coronary cataract with blue punctate opacities.

PURPOSE: To demonstrate the underlying genetic defect that contribute to inherited cataract in a northern Chinese pedigree. METHODS: The study recruited a family pedigree with a diagnosis of bilateral coronary cataract with blue punctate opacities. Fourteen family members and 100 healthy volunteers were enrolled. DNA sample of the proband in this family were analyzed by high-throughput sequencing, which was then demonstrated by Sanger sequencing in the remained people in the family and 100 controls. The functional effect of mutant genes was investigated via bioinformatics analysis, including Polymorphism Phenotyping version2 (PolyPhen-2), Protein Variation Effect Analyzer (PROVEAN v1.1.3) Scale-Invariant Feature Transform (SIFT), and Mutation Taster. RESULTS: In this three-generation family, a novel heterozygous mutation was found in the kinase domain of CRYBA1 gene (c.340C > T, p.R114C), which was only detected in patients in the family with inherited cataract and were not detected in the remained people in the family nor in normal people. The pathogenic effect of the mutation was verified via bioinformatics analysis. CONCLUSION: Our study presented the molecular experiments to confirm that a novel missense mutation of c.340 C > T located in exon 4 of CRYBA1 gene results in a bilateral coronary cataract with blue punctate opacities, which enriches the mutation spectrum of CRYBA1 gene in inherited cataract and deepens the understanding of the pathogenesis of inherited cataract.

Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia.

Background: Previous studies have reported that biomarkers of liver injury and renal dysfunction were associated with hypertensive disorders of pregnancy (HDP). However, the associations of these biomarkers in early pregnancy with the risk of HDP and longitudinal blood pressure pattern during pregnancy were rarely investigated in prospective cohort studies. Methods: A total of 1,041 pregnant women were enrolled in this prospective cohort study. BP was assessed in four stages throughout pregnancy. The following biomarkers were measured at early pregnancy before 18 weeks gestation: lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), and estimated glomerular filtration rate (eGFR). Linear mixed-effects and logistic regression models were used to examine the associations of these biomarkers with longitudinal BP pattern during pregnancy and HDP incidence, respectively. Results: In unadjusted models, higher serum UA, GGT, ALP, and LDH levels, as well as lower eGFR and AST/ALT, were associated with higher BP levels during pregnancy and an increased risk of HDP. After adjustment for maternal age, pre-pregnancy BMI and other potential confounders, UA, GGT, ALP, and LDH remained positively associated with both BP and HDP. However, eGFR and AST/ALT were not associated with HDP after adjusting for potential confounders. When including all 6 biomarkers simultaneously in multivariable analyses, increased UA, GGT, and ALP significantly associated with gestational hypertension and preeclampsia. Conclusion: This study suggests that increased UA, GGT, and ALP in early-pregnancy are independent risk factors of gestational hypertension and preeclampsia.

Negative association between serum adropin and hypertensive disorders complicating pregnancy.

Objective: Study the association of adropin and hypertensive disorders complicating pregnancy (HDCP). Methods: Patients with HDCP were matched with normotensive women (47 pairs). Adropin concentrations were detected by enzyme-linked immunosorbent assay. Results: Compared with the controls, the serum adropin levels were lower in the HDCP group (P < 0.001) and in HDCP subgroups (gestational hypertension, mild preeclampisa, and severe preeclampsia, term, preterm, early onset, and late onset) (all P < 0.05). After adjustment for confounders, adropin remained negatively associated with HDCP (P = 0.027). Conclusion: Lower adropin concentration is significantly associated with HDCP, suggesting that higher or normal adropin levels may be protective against HDCP.

Deep targeted sequencing reveals the diversity of TRB-CDR3 repertoire in patients with preeclampsia.

Preeclampsia (PE) is one of the major causes of maternal and perinatal mortality worldwide. This study aimed to determine the immunological characteristics of PE patients and normal pregnancy at the T cell receptor beta-chain (TRB) level by using high-throughput sequencing. High-throughput sequencing was performed to analyze the expression of TRB-CDR3 in circulating T cells. T cells were isolated from 36 healthy pregnant women, 24 patients with severe PE, and 18 patients with moderate PE. Rearranged mRNA sequences were assigned to their germline V, D, and J counterparts, and translated into proper amino acids by the IMGT database. In general, PE samples had more TRB-CDR3 reads and types than those of normal pregnant woman in the circulation, but the mean number of TRB-CDR3 reads and unique TRB-CDR3 reads in severe group was lower than that in the moderate group. In PE patients, the V7_9 and V20_1 gene loci were more prevalent than in healthy pregnant women. In addition, 4 kinds of TRB-CDR3 peptides were found to be highly relevant to the pathogenesis of PE. Of them, peptides matched to herpes simplex virus antigen-specific T cells were much lower in PE samples.

High-Throughput Sequencing Reveals Immunological Characteristics of the TRB-/IgH-CDR3 Region of Umbilical Cord Blood.

OBJECTIVE: To compare the differences of immunological characteristics between newborn and adults, we performed high-throughput sequencing to reveal the diversity of umbilical cord blood and adult peripheral blood at both T-cell receptor beta chain (TRB) and immunoglobulin heavy chain (IGH) levels. STUDY DESIGN: High-throughput sequencing was performed to analyze the expression of TRB-CDR3 and IGH-CDR3 in circulating T and B cells isolated from 20 healthy adults, 56 pregnant women, and 40 newborns. RESULTS: Our results revealed different immunological characteristics between newborn and adults, such as distinctive complementarity determining region 3 (CDR3) lengths, usage bias of variable and joining segments, random nucleotide addition, a large number of unique CDR3 peptides, and a greater repertoire diversity. Moreover, each newborn had a distinctive TRB-/IGH-CDR3 repertoire that was independent of the maternal immune status. CONCLUSIONS: This study presents comprehensive, unrestricted profiles of the TRB/IGH-CDR3 repertoire of newborns, pregnant women, and healthy adults at a sequence-level resolution. Our data may contribute to a better understanding of the immune system of newborns and benefit the efficient application of umbilical cord blood transplantation in future.