Whole-genome resequencing uncovers diversity and selective sweep in Kazakh cattle.

The Kazakh cattle in the Xinjiang Uygur Autonomous Region of China are highly adaptable and have multiple uses, including milk and meat production, and use as draft animals. They are an excellent original breed that could be enhanced by breeding and hybrid improvement. However, the genomic diversity and signature of selection underlying the germplasm characteristics require further elucidation. Herein, we evaluated 26 Kazakh cattle genomes in comparison with 103 genomes of seven other cattle breeds from regions around the world to assess the Kazakh cattle genetic variability. We revealed that the relatively low linkage disequilibrium at large SNP distances was strongly correlated with the largest effective population size among Kazakh cattle. Using population structural analysis, we next demonstrated a taurine lineage with restricted Bos indicus introgression among Kazakh cattle. Notably, we identified putative selected genes associated with resistance to disease and body size within Kazakh cattle. Together, our findings shed light on the evolutionary history and breeding profile of Kazakh cattle, as well as offering indispensable resources for germplasm resource conservation and crossbreeding program implementation.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Research on the perception of the terrain image of the tourism destination based on multimodal user-generated content data.

Destination image is a powerful means by which destinations compete in the tourism industry, and the accurate identification of a destination image better serves destination marketing and management. This study uses multimodal data, such as text, images, and videos uploaded by tourists, to construct a comprehensive and systematic destination image process. The "cognitive-emotional-overall image" model, latent Dirichlet allocation (LDA) model, and deep residual neural networks are implemented to build a framework to examine the perception of a destination image, travelogues, and short videos from the sources called Ctrip, Qunar, and TikTok. The results show that tourists' overall perception of Sanya is based mainly on the cognitive image of natural scenery, human resources, and food. In addition, there are differences between textual and visual cognitive images among the perceptual images when multimodal data is under consideration. Furthermore, tourists have an overall positive affective image of Sanya as a destination.

A meta-analysis of immunogenicity and safety of two versus single-doses of influenza A (H1N1) vaccine in person living with HIV.

Purpose: Influenza vaccination of person living with HIV (PLWH) is a powerful means to tackle severe clinical outcomes. Few data on two doses of influenza vaccine in PLWH are available.Research Design: To evaluate the immunogenicity and safety of two doses of vaccine as compared with single dose in PLWH, we searched Pubmed, Embase, and web of science databases for relevant articles (January 2009 to April 2023). Pooled SMD or RR and 95% CI were calculated.Results: A total of 2436 participants from 14 studies were included. Compared to single dose influenza vaccine regimen, the pooled RR of seroprotection and seroconversion for two doses of vaccines was 1.14 (95%CI: 1.08-1.21) and 1.25 (95%CI: 1.16-1.34), respectively; the SMD of GMT was 0.42 (95%CI: 0.35, 0.49). Regarding safety, the fever risk in PLWH receiving two doses of vaccine was 3.42 fold higher than that of single dose vaccine, and the risk of myalgia had a quarter reduction. No serious vaccine-related adverse events were reported.Conclusions: Collectively, two doses of the vaccine are associated with a better immunogenicity and an acceptable safety in PLWH. Two doses of the adjuvant vaccination might be a superior vaccination regimen.nation regimen.

Molecular mechanism of Hfq-dependent sRNA1039 and sRNA1600 regulating antibiotic resistance and virulence in Shigella sonnei.

Bacillary dysentery caused by Shigella spp. is a significant concern for human health. Small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella spp. However, the specific mechanisms behind this phenomenon are still not fully understood. This study discovered two sRNAs (sRNA1039 and sRNA1600) that may be involved in bacterial resistance and virulence. By constructing deletion mutants (WT/ΔSR1039 and WT/ΔSR1600), this study found that the WT/ΔSR1039 mutants caused a two-fold increase in sensitivity to ampicillin, gentamicin and cefuroxime, and the WT/ΔSR1600 mutants caused a two-fold increase in sensitivity to cefuroxime. Furthermore, the WT/ΔSR1600 mutants caused a decrease in the adhesion and invasion of bacteria to HeLa cells (P<0.01), and changed the oxidative stress level of bacteria to reduce their survival rate (P<0.001). Subsequently, this study explored the molecular mechanisms by which sRNA1039 and sRNA1600 regulate antibiotic resistance and virulence. The deletion of sRNA1039 accelerated the degradation of target gene cfa mRNA and reduced its expression, thereby regulating the expression of pore protein gene ompD indirectly and negatively to increase bacterial sensitivity to ampicillin, gentamicin and cefuroxime. The inactivation of sRNA1600 reduced the formation of persister cells to reduce resistance to cefuroxime, and reduced the expression of type-III-secretion-system-related genes to reduce bacterial virulence by reducing the expression of target gene tomB. These results provide new insights into Hfq-sRNA-mRNA regulation of the resistance and virulence network of Shigella sonnei, which could potentially promote the development of more effective treatment strategies.

Intrauterine phenotype features of fetuses with 7q11.23 microduplication syndrome.

OBJECTIVE: To share our experience on prenatal diagnosis of 7q11.23 microduplication syndrome and to further delineate the fetal phenotypes of the syndrome. METHODS: A retrospective study was conducted to evaluate seven cases of dup7q11.23 syndrome diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA results, pregnancy outcomes and follow-ups. RESULTS: Seven cases, including 2 pairs of MCDA twins, were prenatally identified with dup7q11.23 syndrome. The most common prenatal sonographic features were ventriculomegaly, low-lying conus medullaris, and dilated ascending aorta. All 7 fetuses presented with typical 7q11.23 duplications (1.40-1.55 Mb). Parental chromosome analysis was performed in four pairs of parents, and indicated that the duplications of Case 6 and 7 were inherited from their asymptomatic mother. CONCLUSION: Our case series suggest that prenatal features of dup7q11.23 cases are diversified, with ventriculomegaly and low-lying conus medullaris being the most common intrauterine phenotypes. Additionally, cleft palate, dilated ascending aorta, and renal abnormalities were also observed, and should be taken into consideration in subsequent studies.

Infantile fibrosarcoma of the perineum with dorsal metastasis in a neonate: a case report original.

BACKGROUND: Infantile fibrosarcoma is a rare pediatric soft tissue tumor and usually appears in children before one year of age. Distal extremities constitute the most frequently affected locations, and other tissues such as the trunk, head and neck, gut, sacrococcygeal region, and viscera are uncommon sites. CASE PRESENTATION: We describe a rare case of infantile fibrosarcoma arising from the perineum. First, a cystic mass was detected using prenatal ultrasonography, and then an echo was changed in serial ultrasound examinations. A solid cystic lesion was found at term; a hypoechoic lesion occurred in the back. The tumor became so large that massive bleeding occurred, which then underwent surgical resection. Pathological examination confirmed infantile fibrosarcoma. CONCLUSION: Our report demonstrates not all ultrasonographic findings in cases of infantile fibrosarcoma exhibit a solid mass during the initial examination - an early-stage lesion may reveal a cystic echo. Infantile fibrosarcoma has a good prognosis and surgery constitute the main treatment, with adjuvant chemotherapy being received if necessary.

Prenatal phenotype features and genetic etiology of the Williams-Beuren syndrome and literature review.

Objective: To share our experience on prenatal diagnosis of Williams-Beuren syndrome(WBS) and to improve the awareness, diagnosis, and intrauterine monitoring of the fetuses of this disease. Methods: The study retrospectively evaluated 14 cases of WBS diagnosed prenatally by single nucleotide polymorphism array (SNP-array). Clinical data from these cases were systematically reviewed, including maternal demographics, indications for invasive prenatal diagnosis, ultrasound findings, SNP-array results, trio-medical exome sequencing (Trio-MES) results, QF-PCR results, pregnancy outcomes and follow-ups. Results: A total of 14 fetuses were diagnosed with WBS and their prenatal phenotypes were assessed retrospectively. In our case series, the most common ultrasound features were intrauterine growth retardation (IUGR), congenital cardiovascular defects, abnormal fetal placental doppler indices, thickened nuchal translucency(NT) and polyhydramnios. Other less common ultrasound features include fetal hydrops, hydroderma, bilateral pleural effusion, subependymal cysts, etc. Parental chromosome analysis was performed in seven pairs of parents, and all the deletions on chromosome 7q11.23 were de novo. Conclusion: Prenatal ultrasound features of WBS cases are highly variable, with IUGR, cardiovascular abnormalities and abnormal fetal placental doppler indices, being the most common intrauterine phenotypes. Our case series expand the intrauterine phenotypes of WBS, including cardiovascular abnormalities right aortic arch(RAA) combined with persistent right umbilical vein(PRUV) and elevated the ratio of end-systolic peak flow velocity to end-diastonic peak flow velocity(S/D). In the meantime, with the decrease in the cost of the next-generation sequencing, the method may become widely used in prenatal diagnosis in the near future.

Involvement of RNA chaperone hfq in the regulation of antibiotic resistance and virulence in Shigella sonnei.

The host factor for RNA phage Qß replicase (Hfq) is a crucial post-transcriptional regulator in many bacterial pathogens, facilitating the interaction between small non-coding RNAs (sRNAs) and their target mRNAs. Studies have suggested that Hfq plays a role in antibiotic resistance and virulence in bacteria, although its functions in Shigella are not fully understood. In this study, we investigated the functional roles of Hfq in Shigella sonnei (S. sonnei) by constructing an hfq deletion mutant. Our phenotypic assays showed that the hfq deletion mutant was more sensitivity to antibiotics and had impaired virulence. Transcriptome analyses supported the results concerning the phenotype of the hfq mutant and showed that differentially expressed genes were mainly enriched in the KEGG pathways two-component system, ABC transporters, ribosome, and Escherichia coli biofilm formation. Additionally, we predicted eleven novel Hfq-dependent sRNAs, which were potentially involved in the regulation of antibiotic resistance and/or virulence in S. sonnei. Our findings suggest that Hfq plays a post-transcriptional role in regulating antibiotic resistance and virulence in S. sonnei, and could provide a basis for future studies on Hfq-sRNA-mRNA regulatory networks in this important pathogen.

Genome-wide identification and analysis of TMT-based proteomes in longissimus dorsi tissue from Kazakh cattle and Xinjiang brown cattle.

With the gradual completion of the human genome project, proteomes have gained extremely important value in the fields of human disease and biological process research. In our previous research, we performed transcriptomic analyses of longissimus dorsi tissue from Kazakh cattle and Xinjiang brown cattle and conducted in-depth studies on the muscles of both species through epigenetics. However, it is unclear whether differentially expressed proteins in Kazakh cattle and Xinjiang brown cattle regulate muscle production and development. In this study, a proteomic analysis was performed on Xinjiang brown cattle and Kazakh cattle by using TMT markers, HPLC classification, LC/MS and bioinformatics analysis. A total of 13,078 peptides were identified, including 11,258 unique peptides. We identified a total of 1874 proteins, among which 1565 were quantifiable. Compared to Kazakh cattle, Xinjiang brown cattle exhibited 75 upregulated proteins and 44 downregulated proteins. These differentially expressed proteins were enriched for the functions of adrenergic signaling in cardiomyocytes, fatty acid degradation and glutathione metabolism. In our research, we found differentially expressed proteins in longissimus dorsi tissue between Kazakh cattle and Xinjiang brown cattle. We predict that these proteins regulate muscle production and development through select enriched signaling pathways. This study provides novel insights into the roles of proteomes in cattle genetics and breeding.

Anxiety, depression, insomnia symptoms & associated factors among young to middle-aged adults during the resurgent epidemic of COVID-19: a cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic is a public health emergency of international concern. However, its stress on the mental health of young to middle-aged adults is largely unexplored. This study aimed to evaluate the mental health difficulties during the resurgent phase of COVID-19 among young to middle-aged adults in China. There were 1,478 participants with a median age of 26 years (IQR, 23 - 30), including 535 males (36.2%). The prevalence of anxiety, depression, and insomnia were 8.6%, 11.4%, and 13.7%, respectively. Participants aged 29 - 59 years (OR, 95% CI: 2.46, 1.23 - 4.91) and females (2.49, 1.55 - 4.01) had a higher risk of anxiety. Education status, worried level about the current COVID-19, and the level of COVID-19's impact on life were significantly associated with the prevalence of anxiety. Besides, the level of COVID-19's impact on life was positively related to the prevalence of depression and insomnia. Our study provided novel evidence of psychological difficulties among young to middle-aged adults during the resurgent stage of the COVID-19 epidemic. Psychological intervention should be continuously implemented to prevent long-term psychological comorbidities during the COVID-19 epidemic.

Comparative genomic analysis of Escherichia coli strains obtained from continuous imipenem stress evolution.

The carbapenem-resistant Escherichia coli has aroused increasing attention worldwide, especially in terms of imipenem (IMP) resistance. The molecular mechanism of IMP resistance remains unclear. This study aimed to explore the resistance mechanisms of IMP in E. coli. Susceptible Sx181-0-1 strain was induced into resistance strains by adaptive laboratory evolution. The drug resistance spectrum was measured using the disk diffusion and microbroth dilution methods. Whole-genome sequencing and resequencing were used to analyze the nonsynonymous single-nucleotide polymorphisms (nsSNPs) between the primary susceptible strain and resistant strains. The expression levels of these genes with nsSNPs were identified by real-time quantitative PCR (RT-qPCR). Resistance phenotype appeared in the induced 15th generation (induction time = 183 h). Sx181-32 and Sx181-256, which had the minimum inhibitory concentrations of IMP of 8 and 64 µg ml-1, were isolated during continuous subculture exposed to increasing concentrations of IMP, respectively. A total of 19 nsSNPs were observed both in Sx181-32 and Sx181-256, distributed in rpsU, sdaC, zwf, ttuC, araJ, dacC, mrdA, secF, dacD, lpxD, mrcB, ftsI, envZ, and two unknown function genes (orf01892 and orf01933). Among these 15 genes, five genes (dacC, mrdA, lpxD, mrcB, and ftsI) were mainly involved in cell wall synthesis. The mrdA (V338A, L378P, and M574I) and mrcB (P784L, A736V, and T708A) had three amino acid substitutions, respectively. The expression levels of rpsU, ttuC, and orf01933 were elevated in both Sx181-32 and Sx181-256 compared to Sx181-0-1. The expression levels of these genes were elevated in Sx181-256, except for araJ. Bacteria developed resistance to antimicrobials by regulating various biological processes, among which the most involved is the cell wall synthesis (dacC, mrdA, lpxD, mrcB, and ftsI). The combination mutations of mrdA, envZ, and ftsI genes may increase the resistance to IMP. Our study could improve the understanding of the molecular mechanism of IMP resistance in E. coli.

Estrogen Attenuates Chronic Stress-Induced Cardiomyopathy by Adaptively Regulating Macrophage Polarizations via ß2-Adrenergic Receptor Modulation.

Clinical demographics have demonstrated that postmenopausal women are predisposed to chronic stress-induced cardiomyopathy (CSC) and this has been associated with the decrease of estrogen. Meanwhile, recent studies have implicated unsolved myocardial proinflammatory responses, which are characterized by enormous CD86+ macrophage infiltrations as an underlying disease mechanism expediting the pathological remodeling of the heart during chronic stress. However, we had previously demonstrated that estrogen confers cardioprotection via the modulation of cardiomyocytes ß2-adrenoceptors (ß2AR)-Gs/Gi pathways during stress to lessen the incidence of stress-induced cardiovascular diseases in premenopausal women. Intriguingly, macrophages express ß2AR profoundly as well; as such, we sought to elucidate the possibilities of estrogen modulating ß2AR-Gs/Gi pathway to confer cardioprotection during stress via immunomodulation. To do this, ovariectomy (OVX) and sham operations (Sham) were performed on female Sprague-Dawley (SD) rats. Two weeks after OVX, the rats were injected with 40 µg/kg/day of estradiol (E2). Next, on day 36 after OVX, chronic stress was induced by a daily subcutaneous injection of 5 mg/kg/day of isoproterenol (ISO). The effect of E2 on relevant clinical cardiac function indexes (LVSP, LVEDP, + dp/dt and -dp/dt), myocardial architecture (cardiomyocyte diameter and fibrosis), ß2AR alterations, and macrophage (CD86+ and CD206+) infiltrations were assessed. In vitro, peritoneal macrophages (PMΦ) were isolated from wild-type and ß2AR-knockout female mice. The PMΦ were treated with ISO, E2, and ß2AR blocker ICI 118,551 for 24 h, and flow cytometric evaluations were done to assess their phenotypic expression. E2 deficiency permitted the induction of CSC, which was characterized by cardiac dysfunctions, maladaptive myocardial hypertrophy, unresolved proinflammatory responses, and fibrosis. Nonetheless, E2 presence/supplementation during stress averted all the aforementioned adverse effects of chronic stress while preventing excessive depletion of ß2AR. Also, we demonstrated that E2 facilitates timely resolution of myocardial proinflammation to permit reparative functions by enhancing the polarization of CD86+ to CD206+ macrophages. However, this adaptive immunomodulation is hampered when ß2AR is inhibited. Taken together, the outcomes of this study show that E2 confers cardioprotection to prevent CSC via adaptive immunomodulation of macrophage phenotypes, and ß2AR-mediated signaling is crucial for the polarizations of CD86+ to CD206+ macrophages.

The incubation period of COVID-19: a global meta-analysis of 53 studies and a Chinese observation study of 11 545 patients.

BACKGROUND: The incubation period is a crucial index of epidemiology in understanding the spread of the emerging Coronavirus disease 2019 (COVID-19). In this study, we aimed to describe the incubation period of COVID-19 globally and in the mainland of China. METHODS: The searched studies were published from December 1, 2019 to May 26, 2021 in CNKI, Wanfang, PubMed, and Embase databases. A random-effect model was used to pool the mean incubation period. Meta-regression was used to explore the sources of heterogeneity. Meanwhile, we collected 11 545 patients in the mainland of China outside Hubei from January 19, 2020 to September 21, 2020. The incubation period fitted with the Log-normal model by the coarseDataTools package. RESULTS: A total of 3235 articles were searched, 53 of which were included in the meta-analysis. The pooled mean incubation period of COVID-19 was 6.0 days (95% confidence interval [CI] 5.6-6.5) globally, 6.5 days (95% CI 6.1-6.9) in the mainland of China, and 4.6 days (95% CI 4.1-5.1) outside the mainland of China (P = 0.006). The incubation period varied with age (P = 0.005). Meanwhile, in 11 545 patients, the mean incubation period was 7.1 days (95% CI 7.0-7.2), which was similar to the finding in our meta-analysis. CONCLUSIONS: For COVID-19, the mean incubation period was 6.0 days globally but near 7.0 days in the mainland of China, which will help identify the time of infection and make disease control decisions. Furthermore, attention should also be paid to the region- or age-specific incubation period.

New sonographic feature (C-sign) to improve the prenatal accuracy of jejunal atresia.

OBJECTIVES: To describe a new sonographic feature of the C-sign for prenatal diagnosis of jejunal atresia and evaluate its role in prenatal jejunal atresia, particularly preceding bowel dilatation and polyhydramnios. METHODS: This was a retrospective study from a tertiary maternal hospital. Patients with prenatal sonographic examination and confirmed small bowel atresia postdelivery were included. All sonographic images were reviewed by two senior sonographers. Comparison of sonographic images between prenatal jejunal and ileal atresia using the C-sign resembles the shape of the entire duodenum and other traditional sonographic features. The control group without bowel atresia was assessed for the presence of the C-sign. RESULTS: The C-sign and combined bowel dilatation with polyhydramnios were more frequent in jejunal atresia than ileal atresia, but the C-sign can be used to detect jejunal atresia earlier. The C-sign can be more likely to diagnose jejunal atresia in persisting bowel dilatation and polyhydramnios. The C-sign was not reported in any of the control fetuses. CONCLUSION: The C-sign is a new sonographic feature that can be used to improve the prenatal accuracy and early detection of jejunal atresia. However, further prospective validation is needed.

SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients.

Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions without known CHD genes suggests unknown CHD genes within these intervals. Here, we have shown that knockdown of SORBS2, a 4q interval gene, disrupted sarcomeric integrity of cardiomyocytes and caused reduced cardiomyocyte number in human embryonic stem cell differentiation model. Molecular analyses revealed decreased expression of second heart field (SHF) marker genes and impaired NOTCH and SHH signaling in SORBS2-knockdown cells. Exogenous SHH rescued SORBS2 knockdown-induced cardiomyocyte differentiation defects. Sorbs2-/- mouse mutants had atrial septal hypoplasia/aplasia or double atrial septum (DAS) derived from impaired posterior SHF with a similar expression alteration. Rare SORBS2 variants were significantly enriched in a cohort of 300 CHD patients. Our findings indicate that SORBS2 is a regulator of SHF development and its variants contribute to CHD pathogenesis. The presence of DAS in Sorbs2-/- hearts reveals the first molecular etiology of this rare anomaly linked to paradoxical thromboembolism.

Combined transcriptome and proteome analyses reveal differences in the longissimus dorsi muscle between Kazakh cattle and Xinjiang brown cattle.

OBJECTIVE: With the rapid development of proteomics sequencing and RNA sequencing technology, multi-omics analysis has become a current research hotspot. Our previous study indicated that Xinjiang brown cattle have better meat quality than Kazakh cattle. In this study, Xinjiang brown cattle and Kazakh cattle were used as the research objects. METHODS: Proteome sequencing and RNA sequencing technology were used to analyze the proteome and transcriptome of the longissimus dorsi muscle of the two breeds of adult steers (n = 3). RESULTS: In this project, 22,677 transcripts and 1,874 proteins were identified through quantitative analysis of the transcriptome and proteome. By comparing the identified transcriptome and proteome, we found that 1,737 genes were identified at both the transcriptome and proteome levels. The results of the study revealed 12 differentially expressed genes and proteins: troponin I1, crystallin alpha B, cysteine, and glycine rich protein 3, phosphotriesterase-related, myosin-binding protein H, glutathione s-transferase mu 3, myosin light chain 3, nidogen 2, dihydropyrimidinase like 2, glutamate-oxaloacetic transaminase 1, receptor accessory protein 5, and aspartoacylase. We performed functional enrichment of these differentially expressed genes and proteins. The Kyoto encyclopedia of genes and genomes results showed that these differentially expressed genes and proteins are enriched in the fatty acid degradation and histidine metabolism signaling pathways. We performed parallel reaction monitoring (PRM) verification of the differentially expressed proteins, and the PRM results were consistent with the sequencing results. CONCLUSION: Our study provided and identified the differentially expressed genes and proteins. In addition, identifying functional genes and proteins with important breeding value will provide genetic resources and technical support for the breeding and industrialization of new genetically modified beef cattle breeds.

A novel 1p33p32.2 deletion involving SCP2, ORC1, and DAB1 genes in a patient with craniofacial dysplasia, short stature, developmental delay, and leukoencephalopathy: A case report.

INTRODUCTION: Microdeletion syndromes occur from deletion of 5Mb of a chromosome in approximately 5% of patients with unexplained intellectual disability. Interstitial microdeletions at bands 1p33 and 1p32.2 of the short arm of chromosome 1 are rare and have not been previously reported in relation to disease. PATIENT CONCERNS: We present a case of a 39-month boy with Pierre Robin sequence, development delay/intellectual disability, growth retardation, short stature, leukoencephalopathy, craniofacial dysplasia, and speech delay. The child was referred to the Child health care department in October 2014 for his delayed language development and aggravated aggression. DIAGNOSIS: Molecular diagnostic testing with G-band karyotyping was normal but clinical microarray analysis detected a 10 Mb microdeletion at 1p33p32.2. INTERVENTIONS: The patient received rehabilitation. OUTCOMES: Three candidate genes were pinpointed to the deleted area, including ORC1, SCP2, and DAB1. Phenotype-genotype analysis suggested that these three genes are likely to be responsible for the main phenotypes observed in the patient, such as microcephaly, growth retardation, short stature, leukoencephalopathy, and development delay/intellectual disability. CONCLUSIONS: The spectrum of phenotypes this case presented with are likely to be caused by 1p33p32.2 deletion which could represent a new microdeletion syndrome.

[Identification of ATP7B gene variant by combined use of Sanger sequencing, array CGH and quantitative PCR].

OBJECTIVE: To identify the type and origin of ATP7B gene mutation in a family affected with Wilson disease by combined use of multiple methods. METHODS: Peripheral blood samples were collected from the proband, her parents and her brother. Sanger sequencing were used to detect point mutation and small deletion/insertion of the 21 exons and flanking sequences of the ATP7B gene in all family members. Array-based comparative genomic hybridization (aCGH) was performed to identify copy number variations (CNVs) of the ATP7B gene in the proband. The result was validated by quantitative PCR (qPCR) in other 3 members. RESULTS: Sanger sequencing indicated that the proband carried a heterozygous variation c.2668G>A (p.V890M) derived from her mother. In addition, 5 common SNPs were detected in her mother, three of which were also identified in her father and brother. The 5 SNPs in the proband were of the wide type. aCGH analysis demonstrated that the proband was heterozygous for a 4 kb deletion, which encompassed exons 2 and 3 of the ATP7B gene and 2 SNPs. qPCR showed that the copy number in her father and brother was about half of the control, indicating heterozygous loss of exons 2 and 3. CONCLUSION: The combined Sanger sequencing, array CGH and qPCR has identified a novel CNV involving the ATP7B gene. The strategy can improve the diagnostic rate for hereditary or rare diseases.

Pathological cardiac hypertrophy: the synergy of adenylyl cyclases inhibition in cardiac and immune cells during chronic catecholamine stress.

Response to stressors in our environment and daily lives is an adaptation conserved through evolution as it is beneficial in enhancing the survival and continuity of humans. Although stressors have evolved, the drastic physiological response they elicit still remains unchanged. The chronic secretion and circulation of catecholamines to produce physical responses when they are not required may result in pathological consequences which affect cardiac function drastically. This review seeks to point out the probable implication of chronic stress in inducing an inflammation disorder in the heart. We discussed the likely synergy of a G protein-independent stimuli signaling via ß2-adrenergic receptors in both cardiomyocytes and immune cells during chronic catecholamine stress. To explain this synergy, we hypothesized the possibility of adenylyl cyclases having a regulatory effect on G protein-coupled receptor kinases. This was based on the negative correlations they exhibit during normal cardiac function and heart failures. As such, the downregulation of adenylyl cyclases in cardiomyocytes and immune cells during chronic catecholamine stress enhances the expressions of G protein-coupled receptor kinases. In addition, we explain the maladaptive roles played by G protein-coupled receptor kinase and extracellular signal-regulated kinase in the synergistic cascade that pathologically remodels the heart. Finally, we highlighted the therapeutic potentials of an adenylyl cyclases stimulator to attenuate pathological cardiac hypertrophy (PCH) and improve cardiac function in patients developing cardiac disorders due to chronic catecholamine stress.