Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women.

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA. Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR. Result: Among the 39,647 participants who were screened, 726 participants were the carriers of SMN1. The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening. Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions.

[Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China]. / ç”˜è‚ƒåœ°åŒºé—ä¼ ä»£è°¢ç— ç–¾ç— è°±åŠè‡´ç— åŸºå› åˆ†æž.

OBJECTIVES: To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China. METHODS: A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination. RESULTS: A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance. CONCLUSIONS: This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Analysis of endophyte diversity of Gentiana officinalis among different tissue types and ages and their association with four medicinal secondary metabolites.

Background: The difference of metabolites in medicinal plants has always been concerned to be influenced by external environmental factors. However, the relationship between endophytes and host metabolites remains unclear. Methods: In this study, we used 16S and ITS amplicon sequencing to compare endophyte diversity among different tissue types and ages of Gentiana officinalis. Endophyte diversity and abundance was also analyzed in relation to the abundance of four secondary metabolites (Gentiopicroside, Loganic acid, Swertiamarine and Sweroside). Results: The diversity and richness of G. officinalis endophyte differed as a function of tissue types and ages. Four metabolites of G. officinalis were significantly correlated with the abundance of dominant endophyte genera. The predictive function analysis showed that metabolism was main function of endophytic bacteria in different tissue and year root samples, while saprotroph was dominant trophic modes of endophytic fungi in the different year root samples. The dominant trophic modes of endophytic fungi was saprotroph and pathotroph, and relative abundances differed in the different tissue samples. The results of this study will help to elucidate the plant-microbial interactions and provide key information on the role of endophytes in the production of G.officinalis and its important metabolites.

The Mutation Analysis of the AMT Gene in a Chinese Family With Nonketotic Hyperglycinemia.

Background: Nonketotic hyperglycinemia is a metabolic disease with autosomal recessive inheritance due to the glycine cleavage system (GCS) defect leading to the accumulation of glycine that causes severe and fatal neurological symptoms in the neonatal period. Methods: Genomic DNA was extracted from the peripheral blood of the female proband and her family members. The AMT variation was detected in the patient by whole-exome sequencing (WES), and the variant was validated by Sanger sequencing. Results: The WES showed that there were novel compound heterozygous frameshift variations c.977delA (p.Glu326Glyfs*12) and c.982_983insG (p.Ala328Glyfs*22) in exon eight of the AMT gene (NM_000481.4) in the proband. Genetic analysis showed that the former was inherited from the mother, and the latter was inherited from the father. Conclusion: We report the novel compound heterozygous variation of the AMT gene in a Chinese girl with NKH by WES, which has never been reported previously. Our case expanded the AMT gene mutation spectrum, further strengthened the understanding of NKH, and deepened the genetic and clinical heterogeneity of the disease. However, the study of treatment and prognosis is still our future challenge and focus.

Analysis of endophyte diversity of two Gentiana plants species and the association with secondary metabolite.

BACKGROUND: The influence of external environmental factors on secondary metabolites of medicinal plants has always been studied. However, little is known about the relationships between endophytes and host metabolites, especially the relationship differences between different plant species. Thus, we used high-throughput sequencing methods to compare endophyte diversity from roots of two closely related species, Gentiana officinalis and G. siphonantha, from the same production area, and analyze the association with four secondary metabolites (Gentiopicroside, Loganic acid, Swertiamarine and Sweroside). RESULTS: The fungal and bacteria communities' richness and diversity of G. siphonantha was higher than G. officinalis. Ascomycota and Proteobacteria were dominant fungal and bacterial phylum of the two closely related species. At the genus level, Tetracladium and Cadophora were dominant fungal genus in G. officinalis and G. siphonantha samples, respectively. While Pseudomonas was dominant bacterial genus in two closely related species, with relative abundances were 8.29 and 8.05%, respectively. Spearman analysis showed that the content of loganic acid was significantly positively correlated with endophytic fungi, the content of gentiopicroside, swertiamarine and sweroside were significantly positively correlated with endophytic bacteria in the two related species. PICRUSt and FUNGuild predictive analysis indicated that metabolism and saprotroph was primary function of endophytic bacteria and fungi in the two related species. CONCLUSION: Our results will expand the knowledge on relationships of plant-microbe interactions and offer pivotal information to reveal the role of endophytes in the production of Gentiana plant and its important secondary metabolite.

Range expansion decreases the reproductive fitness of Gentiana officinalis (Gentianaceae).

Plants living at the edge of their range boundary tend to suffer an overall decline in their fitness, including growth and reproduction. However, the reproductive performance of plants in artificially expanded habitats is rarely investigated, although this type of study would provide a better understanding of range limitations and improved conservation of ex situ plants. In the current study, we transplanted a narrowly dispersed species of Gentiana officinalis H. Smith (Gentianaceae) from its natural area of distribution to two different elevations and natural elevation to comprehensively study its pollination biology, including flowering phenology and duration, floral display, reproductive allocation, pollinator activity, and seed production. The findings indicated that the starting point and endpoint of the flowering phenology of G. officinalis were earlier at the low elevation, but the peak flowering periods did not differ significantly between any of the experimental plots. When transplanted, the flowering duration, especially the female phase, was reduced; the floral display, including spray numbers, flower numbers, and flower size (length and width), decreased, especially at high elevations. Moreover, the pollen numbers and pollen-ovule ratio were decreased at both high and low elevations, although the ovule numbers showed no change, and aboveground reproductive allocation was decreased. Furthermore, pollinator richness and activity were significantly decreased, and the seed-set ratio decreased under both natural conditions and with supplemental pollination. Finally, more severe pollen limitation was found in transplanted individuals. These results indicated an overall decrease in reproductive fitness in plants living outside their original area of distribution when the geographical range of G. officinalis was expanded.

Urbanization threaten the pollination of Gentiana dahurica.

With rapid spread of the urbanization, many environmental factors, such as climate, soil pH and nutrients have been changed. However, the plant pollination affected by urbanization was seldom conducted. Here, we studied the flower visitation rates, seed production, pollen limitation and flower morphological characters of Gentiana dahurica at 3 populations along an urban-peri-urban gradient around Xi'ning over 4 consecutive years, aiming to test the effects of urbanization on plant pollination service. Our results showed that the pollinator visit frequencies, interannual stability of pollinator assemblages and visit frequencies declined with the intensification of urbanization. As urbanization intensified, plant borne more flowers and the flower morphological sizes became "longer" (the length of flowers, filaments and styles were increased, but the width of flowers kept stable at the 3 populations); the flower duration, especially the female phase duration prolonged. The seed-set ratio of G. dahurica in natural condition decreased and more severe pollen limitation occurred in more urbanized populations. Also, an interannual variation of seed-set ratio and index of pollen limitation (IPL), which related with the variation of pollinator visit frequencies, were found in this study. These results suggest that the pollination service can be threatened by urbanization over a long-time interval for G. dahurica. This finding highlights the importance of pollinator affections acting on plant pollination system. Additionally, as pollinator assemblages and visit frequencies interannually changed, a long-time scale observation is needed to understand the plant-pollinator relationships.

The association between rs16917496 T/C polymorphism of SET8 gene and cancer risk in Asian populations: a meta-analysis.

Epidemiological studies have demonstrated close associations between SET8 rs16917496 T/C polymorphism and cancer risk, but the results of published studies were not consistent. We therefore performed this meta-analysis to explore the associations between rs16917496 T/C polymorphism and cancer risk. Five online databases were searched. Odds ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between rs16917496 T/C polymorphism and cancer risk. In addition, heterogeneity, accumulative, sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 13 publications involving 5878 subjects were identified according to included criteria. No significant cancer risk was observed in genetic model of SET8 rs16917496 T/C polymorphism in Asian populations (C vs. T: OR = 1.04, 95%CI = 0.88-1.23, P = 0.63%; TC vs. TT: OR = 1.17, 95%CI = 0.96-1.24, P = 0.11%; CC vs. TT: OR = 0.90, 95%CI = 0.60-1.37, P = 0.63; TC+CC vs. TT: OR = 1.11, 95%CI = 0.90-1.38, P = 0.33; CC vs. TT+TC: OR = 0.92, 95%CI = 0.65-1.30, P = 0.63). Furthermore, similar associations were found in the subgroup analysis of race diversity, control design, genotyping methods, and different cancer types. In summary, our meta-analysis indicated that the SET8 rs16917496 T/C polymorphism may not play a critical role in cancer development in Asian populations.

E2F is involved in radioresistance of carbon ion induced apoptosis via Bax/caspase 3 signal pathway in human hepatoma cell.

Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53-/- cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells. This phenomenon was not observed in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in clonogenic survival, low level of cellular activity, G2 /M phase arrest, promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved-caspase 3 proteins expressions without p53. Changes of E2F1 expressions could partly alter radioresistance in cancer cells. The results were suggested that heavy ion IR could induce p53-/- cancer cells apoptosis via E2F1 signal pathway. Our study provides a scientific rationale for the clinical use of heavy ion as radiotherapy in patients with p53-deficient tumors, which are often resistant to radiotherapy.