Identification of the lateral organ boundary domain gene family and its preservation by exogenous salicylic acid in Cerasus humilis.

The gene family known as the Lateral Organ Boundary Domain (LBD) is responsible for producing transcription factors unique to plants, which play a crucial role in controlling diverse biological activities, including their growth and development. This research focused on examining Cerasus humilis'ChLBD gene, owing to its significant ecological, economic, and nutritional benefits. Examining the ChLBD gene family's member count, physicochemical characteristics, phylogenetic evolution, gene configuration, and motif revealed 41 ChLBD gene family members spread across 8 chromosomes, with ChLBD gene's full-length coding sequences (CDSs) ranging from 327 to 1737 base pairs, and the protein sequence's length spanning 109 (ChLBD30)-579 (ChLBD35) amino acids. The molecular weights vary from 12.068 (ChLBD30) to 62.748 (ChLBD35) kDa, and the isoelectric points span from 4.74 (ChLBD20) to 9.19 (ChLBD3). Categorizing them into two evolutionary subfamilies: class I with 5 branches, class II with 2, the majority of genes with a single intron, and most members of the same subclade sharing comparable motif structures. The results of collinearity analysis showed that there were 3 pairs of tandem repeat genes and 12 pairs of fragment repeat genes in the Cerasus humilis genome, and in the interspecific collinearity analysis, the number of collinear gene pairs with apples belonging to the same family of Rosaceae was the highest. Examination of cis-acting elements revealed that methyl jasmonate response elements stood out as the most abundant, extensively dispersed in the promoter areas of class 1 and class 2 ChLBD. Genetic transcript analysis revealed that during Cerasus humilis' growth and maturation, ChLBD developed varied control mechanisms, with ChLBD27 and ChLBD40 potentially playing a role in managing color alterations in fruit ripening. In addition, the quality of calcium fruit will be affected by the environment during transportation and storage, and it is particularly important to use appropriate means to preserve the fruit. The research used salicylic acid-treated Cerasus humilis as the research object and employed qRT-PCR to examine the expression of six ChLBD genes throughout storage. Variations in the expression of the ChLBD gene were observed when exposed to salicylic acid, indicating that salicylic acid could influence ChLBD gene expression during the storage of fruits. This study's findings lay the groundwork for additional research into the biological role of the LBD gene in Cerasus humilis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01438-5.

Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin 1 Suppression in Female Mice with Increased Anxiety-Like Behaviors.

INTRODUCTION: Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. METHODS: Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor ß (ERß) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. RESULTS: Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and proinflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERß partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. CONCLUSIONS: 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the gastrointestinal tract, alongside inducing anxiety-like behaviors in female mice.

Corrigendum: Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: thoughts on iron supplementation in pregnant women with thalassemia genes.

[This corrects the article DOI: 10.3389/fnut.2022.1005951.].

Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: Thoughts on iron supplementation in pregnant women with thalassemia genes.

Background: There are limited studies on iron-deficiency anemia (IDA) in carriers of various thalassemia genotypes. However, for pregnant women (PW) with high iron demand, ignoring the phenomenon of carrying the thalassemia genes combined with IDA may lead to adverse pregnancy outcomes. Methods: The hematological phenotype indexes of 15,051 PW who received a prenatal diagnosis of thalassemia in our hospital were analyzed, and the plasma ferritin (PF) of 714 anemic pregnant women (APW) was determined. Results: The results showed that 87.43% of APW without thalassemia suffered from IDA. Among APW with various thalassemia genotypes, we found that 40.00∼77.78% of subjects with α-thalassemia silent genotypes [αCS (or QS)α/αα (40.00%), -α3.7(or 4.2)/αα (57.65%), and αWSα/αα (77.78%)] and 18.18∼84.21% of subjects with α-thalassemia minor genotypes [αCS (or QS)α/-α3.7(or 4.2) (18.18%), -α3.7(or 4.2)/-α3.7(or 4.2) (40.00%), αα/-SEA (44.55%), and αWSα/-α3.7(or 4.2) (84.21%)] developed IDA, while in subjects with α-thalassemia intermedia genotypes, only αWSα/-SEA was associated with IDA, with an incidence of 16.67%. However, the incidence of IDA in APW with common ß-thalassemia minor genotypes (ßCD17(A>T)/ß, ßCD41/42 (-TTCT)/ß, ßCD71/72(+A)/ß, ßIVS-II-654(C>T)/ß, and ß-28(A>G)/ß) was less than 10.85%. In addition, the APW with ß-thalassemia minor had a higher PF level than the APW without thalassemia. Conclusion: Our study is the first to reveal differences in the prevalence of IDA among PW with various thalassemia genotypes, indicating that the possibility of IDA should be fully considered when managing PW with α-thalassemia silent or minor genotypes in high-risk areas, and that iron supplementation should be monitored dynamically for PW with ß-thalassemia minor genotypes.

Prevalence and Genetic Analysis of Thalassemia and Hemoglobinopathy in Different Ethnic Groups and Regions in Hainan Island, Southeast China.

Background: There are limited studies on the molecular profile of thalassemia in Hainan, the free trade island in China. Our aim was to reveal the prevalence and molecular mutation spectrum of thalassemia in different ethnic groups and regions of Hainan through a large sample study for the first time. Methods: A total of 231,596 individuals from 19 cities and counties in Hainan were screened by hematological parameter analysis, and further genetic analysis was performed on individuals with MCV less than 82 fL. Results: Totally, 31,780 (13.72%) subjects were diagnosed as thalassemia carriers. The overall prevalence of α-thalassemia, ß-thalassemia, and α+ß-thalassemia were 11.04%, 1.48%, and 1.20%, respectively. We further analyzed the molecular profiles of thalassemia in various ethnic groups and mainly compared the difference between Han and Li. The results showed that the frequency of thalassemia in the Li population (47.03%) was much higher than that in Han (9.37%). Except for ß-thalassemia (1.31% of Li vs. 1.47% of Han), the frequencies of α-thalassemia (39.59% of Li vs. 7.35% of Han) and α+ß-thalassemia (6.13% of Li vs. 0.56% of Han) in the Li were obviously higher than those in Han. The high-frequent genotypes of α-thalassemia in Han were αα/--SEA (25.55%), -α3.7/αα (22.17%), -α4.2/αα (21.59%), αWSα/αα (8.93%), and -α3.7/-α4.2 (4.17%) and those of Li were -α4.2/αα (17.24%), -α3.7/αα (17.16%), -α3.7/-α4.2 (15.09%), αWSα/αα (9.69%), and αWSα/-α3.7 (8.06%), respectively. The αα/--SEA was the highest genotype of α-thalassemia in Han but only accounted for 1.87% in Li. For ß-thalassemia, the top three high-frequent genotypes in both Han and Li were ßCD41/42(-TTCT)/ßN, ß-28(A>G)/ßN, and ßIVS-Ⅱ-654(C>T)/ßN, but the frequency of ßCD41/42(-TTCT)/ßN in Li (90.96%) was much higher than that in Han (56.32%) and the data reported in other provinces of China. Additionally, the prevalence of thalassemia ranged from 8.16% to 34.35% in Hainan, Wuzhishan, Baoting, Qiongzhong, and Baisha have a higher prevalence than other areas. Conclusion: Our study revealed the characteristics of ethnic and regional differences in the prevalence of thalassemia in the childbearing age population of Hainan for the first time, indicating that the prevalence of thalassemia among Li nationality is the highest in China. Those findings will be useful for genetic counseling and the prevention of thalassemia.

Prevalence and genetic analysis of thalassemia in childbearing age population of Hainan, The Free Trade Island in Southern China.

BACKGROUND: Hainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study was to reveal the true prevalence and molecular mutation spectrum of thalassemia in the population of Hainan who are of childbearing age. METHODS: We screened 166,936 individuals from 19 cities and counties in Hainan by hematological parameters analysis, and further conducted genetic analysis for individuals whose MCV was less than 82fL. RESULTS: In total, 21,619 (12.95%) subjects were diagnosed as thalassemia carriers or patients. The overall prevalence of α-thalassemia, ß-thalassemia, and α+ß-thalassemia were 10.39%, 1.38%, and 1.18%, respectively. Eleven α-thalassemia mutations and sixteen ß-thalassemia mutations were identified. The high-frequent genotypes of α-thalassemia were -α3.7 /αα (19.70%), -α4.2 /αα (19.39%), αα/--SEA (15.60%), αWS α/αα (9.24%), and -α3.7 /-α4.2 (8.90%), and those of ß-thalassemia were ßCD41/42(-TTCT) /ßN (58.92%), ß-28(A>G) /ßN (16.05%), ßIVS-Ⅱ-654(C>T) /ßN (8.42%), ßCD71/72(+A) /ßN (6.03%), ßCD17(A>T) /ßN (5.47%), and ßCD26 (GAG>AAG) /ßN (2.69%). In addition, the frequencies and hematological profiles of many rare mutations of α- [Fusion, HKαα, αααanti4.2 , IVS-II-55 (T>G), IVS-II-119 (-G,+CTCGGCCC)] and ß-globin genes [-50 (G>A), IVS-Ⅱ-81 (C>T)] in Hainan were reported for the first time. CONCLUSION: Our study revealed the high prevalence and extensive molecular spectrum of thalassemia in childbearing age population of Hainan, suggesting thalassemia in Hainan ranks second in prevalence among all regions in China. The findings will be useful for genetic counseling and prevention of thalassemia.

Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. RESEARCH IN CONTEXT: Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

[Comparison of the effect of three ß-thalassemia prenatal screening strategies using in Guangdong province].

OBJECTIVE: To compare the effect of three ß-thalassemia prenatal screening strategies in Guangdong province. METHODS: A total of 13 284 hospital-delivered couples and 13 369 newborns were recruited from 91 hospitals in 21 counties or districts of Guangdong province from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were tested for all the couples, and all the couples and newborns were detected by 17 types of ß-globin gene mutations. The effect of three ß-thalassemia prenatal screening strategies were compared as following: (1) MCV/MCH with Hb A2 serial screening (SS): Hb A2 was tested if the woman's MCV < 82 fl and (or) MCH < 27 pg. If the woman's Hb A2 > 3.5, it meant positive. And if the woman was ß-thalassemia carrier and her husband's Hb A2 > 3.5, it meant couple positive. (2) MCV/MCH with Hb A2 parallel screening (PS): if the woman's MCV < 82 fl and (or) MCH < 27 pg and (or) Hb A2 > 3.5 pg, it meant couple positive. And the husband would be tested for ß-globin gene mutations if the woman was ß-thalassemia carrier. (3) MCV/MCH with Hb A2 serial screening for couples (SSC): if one of the couple or both of them had MCV < 82 fl and (or) MCH < 27 pg, the couple would be tested for Hb A2, and if one of the couple got Hb A2 > 3.5, it meant couple positive. RESULTS: (1) For the SS strategy, the sensitivity was 92.69% (583/629); the specificity was 99.87% (12 638/12 655); the positive predictive value was 97.17% (583/600); and the negative predictive value was 99.64% (12 638/12 684). The results of ß-globin gene mutations tested showed that the rate of ß-thalassemia carriers was 4.74% (629/13 284) in the 13 284 pregnant women, and it was 4.29% (570/13 284) in their husbands. (2) The SS strategy detected 27 (0.20%, 27/13 284) ß-thalassemia carrier couples. For the SS strategy detecting ß-thalassemia carrier couples, the missed diagnosis rate was 11.11% (3/27); the sensitivity was 88.89% (24/27); the specificity was 100.00% (27/27); the positive predictive value was 100.00% (24/24); and the negative predictive value was 99.98% (13 257/13 260). (3) When using the SS strategy for 13 369 offsprings, there were 582 ß-thalassemia carriers (4.35%, 582/13369), including 578 (99.31%, 578/582) minor ß-thalassemia, 3 (0.52%, 3/582) intermedia ß-thalassemia and 1 (0.17%, 1/582) major ß-thalassemia. The SS strategy detected 25 fetuses who needed ß-thalassemia prenatal diagnosis. (4) For the PS strategy, the sensitivity was 98.09% (617/629); the specificity was 88.73% (11 229/12 655); the positive predictive value was 30.20% (617/2 043); and the negative predictive value was 99.89% (11 229/11 241). (5) When using the PS strategy for the ß-thalassemia carrier couples, the sensitivity was 100.00% (27/27); the specificity was 95.55% (12 667/13 257); the positive predictive value was 4.38% (27/617); and the negative predictive value was 100.0% (12 667/12 667). (6) The PS strategy detected 28 fetuses who needed ß-thalassemia prenatal diagnosis in 13 369 offsprings. (7) For the SSC strategy, the sensitivity was 93.80% (590/629); the specificity was 95.75% (12 117/12 655); the positive predictive value was 52.30% (590/1 128); and the negative predictive value was 99.68% (12 117/12 156). When the SSC strategy was used for the husbands, the sensitivity was 92.28% (526/570); the specificity was 95.27% (12 112/12 714);the positive predictive value was 46.63% (526/1 128); and the negative predictive value was 99.64% (12 112/12 156). (8) When the SSC strategy was used in ß-thalassemia carrier couples, the sensitivity was 100.00% (27/27); the specificity was 91.69% (12 156/13 257); the positive predictive value was 2.39% (27/1 128); and the negative predictive value was 100.00% (12 156/12 156). (9) The SSC strategy detected 28 fetuses who needed ß-thalassemia prenatal diagnosis. CONCLUSIONS: All the three ß-thalassemia prenatal screening strategies had good effect in clinical practice and public health. While in the high-prone area of ß-thalassemia, MCV/MCH with Hb A2 parallel screening and MCV/MCH with Hb A2 serial screening for couples stratigies were better.

Obstacles to the coordination of delivering integrated prenatal HIV, syphilis and hepatitis B testing services in Guangdong: using a needs assessment approach.

BACKGROUND: Integration of services for Prevention of Mother-To-Child Transmission of HIV (PMTCT) into routine maternal and child health care is promoted as a priority strategy by the WHO to facilitate the implementation of PMTCT. Integration of services emphasizes inter-sectoral coordination in the health systems to provide convenient services for clients. China has been integrating prenatal HIV, syphilis and hepatitis B testing services since 2009. However, as the individual health systems are complex, effective coordination among different health agencies is challenging. Few studies have examined the factors that affect the coordination of such complex systems. The aim of this study is to assess the effectiveness of and examine challenges for integrated service delivery. Findings will provide the basis for strategy development to enhance the effective delivery of integrated services. METHODS: The research was conducted in Guangdong province in 2013 using a needs assessment approach that includes qualitative and quantitative methods. Quantitative data was collected through a survey and from routine monitoring for PMTCT and qualitative data was collected through stakeholder interviews. RESULTS: Routine monitoring data used to assess key indicators of coordination suggested numerous coordination problems. The rates of prenatal HIV (95%), syphilis (47%) and hepatitis B (47%) test were inconsistent. An average of only 20% of the HIV positive mothers was referred in the health systems. There were no regular meetings among different health agencies and the clients indicated complicated service processes. The major obstacles to the coordination of delivering these integrated services are lack of service resource integration; and lack of a mechanism for coordination of the health systems, with no uniform guidelines, clear roles or consistent evaluation. CONCLUSIONS: The key obstacles that have been identified in this study hinder the coordination of the delivery of integrated services. Our recommendations include: 1) Facilitate integration of the funding and information systems by fully combining the service resources of different health agencies into one unit; 2) Establish regular meetings to facilitate exchange of information and address problems; 3) Establish a client referral network between different health agencies with agreed guidelines, clear roles and consistent evaluation.

Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate.

Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio=0.74, P=8.98 × 10(-12)). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.

[Gene diagnosis for a child with tuberous sclerosis].

OBJECTIVE: To identify the pathogenic mutation in a family affected with tuberous sclerosis. METHODS: For the proband and its parents, mutational hotspots in the 11 exons of TSC1 and TSC2 gene were analyzed with DNA sequencing and bioinformatics tools. RESULTS: A heterozygous c.4493G>C missense mutation was identified in the proband. The same mutation was however not found in the parents. CONCLUSION: The missense mutation c.4493G>C probably underlie the tuberous sclerosis complex seen in the child.

High prevalence of thalassemia in migrant populations in Guangdong Province, China.

BACKGROUND: The objectives of this study were to estimate the prevalence of thalassemia and to analyze the need for public health services for migrant populations in different cities in Guangdong Province, China. METHODS: A cross-sectional survey was conducted in 21 cities of Guangdong Province. Twenty-three types of a- and ß-globin gene mutations were detected in a total of 14,230 pregnant women and 14,249 husbands. RESULTS: There was a 16.45% prevalence of thalassemia among the 28,479 individuals, and the prevalences of α-, ß-, and combined α-/ß- thalassemia were 12.03%, 3.80%, and 0.63%, respectively. Compared with the native city residents in the province, the migrants from within the province and the immigrants from outside the province had lower prevalences of thalassemia, but the prevalence values were >11%. CONCLUSIONS: The prevalence values for thalassemia gene mutations were high in all three population groups studied in Guangdong Province. The results indicate that all segments of the Guangdong population should be screened for thalassemia.

Maternal deaths among rural-urban migrants in China: a case-control study.

BACKGROUND: Disparity in maternal mortality exists between rural-urban migrant and urban resident women in China, but little research has provided evidence for related policy development. The objective of this study was to identify associations with and risks for maternal death among rural-urban migrant women in order to improve health services for migrant women and reduce maternal mortality in China. METHODS: We conducted a prospective case-control study in urban areas of Guangdong, Zhejiang and Fujian provinces and Beijing municipality. In each, migrant women who died between July 1, 2010 and October 1, 2011 were identified through reports from China's Maternal and Child Mortality Surveillance System. For each, four matched controls were selected from migrant women who delivered in local hospitals during the same period. We compared socio-demographic characteristics, health status and health service variables between cases and controls, and used bivariate and multivariate conditional logistic regression analyses to determine associations with and risk factors for maternal death. RESULTS: 109 cases and 436 controls were assessed. Family income <2000 yuan per month (OR = 4.5; 95% CI 1.7-11.7) and lack of health insurance (OR = 1.3; 95% CI 1.1-1.6) were more common amongst women who died, as were lack of antenatal care (ANC) (OR = 22.3; 95% CI 4.3-116.0) and attending ANC only 1-4 times (OR = 5.0; 95% CI 1.6-15.5). Knowledge of danger signs during delivery was less common in this group (OR = 0.3; 95% CI 0.1-0.8). CONCLUSION: Differences existed between migrant women who died in pregnancy and surviving controls. The identified risk factors suggest strategies for health sector and community action on reducing maternal mortality among migrant women in China. A systematic approach to maternity care for rural-urban migrant women is recommended.

Genetic counseling and prenatal diagnosis for hereditary hearing loss in high-risk families.

OBJECTIVE: Genetic counseling and prenatal diagnosis are very necessary and accurate to detect hereditary hearing loss, especially in high-risk families. Prenatal diagnosis is testing for diseases or conditions in fetuses before born, which gives parents the chance to prepare psychologically, financially and medically for the probable health and educational needs of the affected neonates. METHODS: 54 unrelated families with children affected with non-syndromic sensorineural hearing loss were enrolled in the study and received genetic analysis with microarray and DNA sequencing technologies. Genetic counseling was provided to each participating families, and prenatal diagnosis was given to those at risk and would like to know their fetuses' genotypes and probable hearing statuses. RESULTS: Half the cases in the present study were diagnosed with confirmed pathogenic mutations and clear inheritance patterns. After receiving genetic counseling, 24 carrier couples with pathogenic mutations chose to proceed prenatal diagnosis, the results of which were in accordance with the pregnancy outcomes. Infants prenatally detected to be monoallelic mutation carriers and those harbored neither deafness-causing mutations form their parents passed newborn hearing screening and six-month follow-ups, while neonates prenatally detected to be carriers of diallelic or compound heterozygous mutations developed hearing loss after birth. CONCLUSIONS: With appropriate genetic counseling and support services provided, the genetic testing and the prenatal diagnosis of hearing loss were valued by carrier couples for the information provided for future family planning and probably the preparation for the health and educational needs of the affected neonates.

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

A prenatal missed diagnosed case of submicroscopic chromosomal abnormalities by karyotyping: the clinical utility of array-based CGH in prenatal diagnostics.

BACKGROUND: Array-based comparative genomic hybridization possesses a number of significant advantages over conventional cytogenetic and other molecular cytogenetic techniques, providing a sensitive and comprehensive detection platform for unexpected imbalances in the genome wide. CASE PRESENTATION: The newborn proband, demonstrated with craniofacial dysmorphism and multiple malformations, was born to a family with spontaneous abortions. This pregnancy was uneventful, except the prenatal ultrasound examination showed an increased nuchal translucency at 12(+) weeks of gestation. Cytogenetics revealed an apparently normal karyotype, and the couple decided to continue the pregnancy. Array-based CGH analysis was applied to the affected infant, identified a combination of 18p deletion and 7q duplication. Further study indicates that the unbalanced translocation was inherited from a balanced translocation carrier parent. CONCLUSIONS: In review of the case, several overlooked points leading to the missed diagnosis should be discussed and certain quality control strategies should be adopted to avoid similar problems in the future. Array-based CGH and karyotyping techniques are complemented by diverse detection spectrum and resolutions, and a combination of these methods could help providing optimal genetic diagnosis. Given that the array-CGH analysis will not introduce additional risk to patients, it is reasonable to recommend those already undergoing invasive testing should take array-based CGH as an adjunct to conventional cytogenetic tests and other molecular cytogenetic analysis.

The association between the polymorphism rs2231142 in the ABCG2 gene and gout risk: a meta-analysis.

Gout is a common metabolic disorder with high heritability. We tried to explore the association between rs2231142 and gout. We searched "rs2231142 or Q141K and gout" in four databases and scholar searching website until 1 June, 2013 and included data from 52,010 participants in meta-analysis and subgroup analysis. The T allele of rs2231142 was associated with increased gout susceptibility (odds ratio [OR] [95 % confidence interval (95 % CI)] = 1.73 [1.55-1.91], P < 0.001). It increased gout risk in Caucasians with OR (95 % CI) = 1.68 (1.50-1.87), P < 0.001; Asians with OR (95 % CI) = 1.93 (1.54-2.31), P < 0.001; Africans with OR (95 % CI) = 1.76 (1.15-2.36), P < 0.001; and New Zealand Pacific Islanders with OR (95 % CI) = 2.94 (1.72-4.15), P < 0.001, but not in New Zealand Maoris, with OR (95 % CI) = 1.12 (0.57-1.67), P = 0.061. No publish or other biases were observed. The T allele of rs2231142 was associated with increased risk of gout.

The prevalence and molecular spectrum of α- and ß-globin gene mutations in 14,332 families of Guangdong Province, China.

OBJECTIVE: To reveal the familial prevalence and molecular variation of α- and ß-globin gene mutations in Guangdong Province. METHODS: A total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters. RESULTS: A high prevalence of α- and ß-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or ß-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or ß-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and ß-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers. CONCLUSIONS: There was a high prevalence of α- and ß-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.