Sex difference in nocturnal blood pressure dipping in adolescents with varying degrees of adiposity.

BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

NLRRC: A Novel Clustering Method of Jointing Non-Negative LRR and Random Walk Graph Regularized NMF for Single-Cell Type Identification.

The development of single-cell RNA sequencing (scRNA-seq) technology has opened up a new perspective for us to study disease mechanisms at the single cell level. Cell clustering reveals the natural grouping of cells, which is a vital step in scRNA-seq data analysis. However, the high noise and dropout of single-cell data pose numerous challenges to cell clustering. In this study, we propose a novel matrix factorization method named NLRRC for single-cell type identification. NLRRC joins non-negative low-rank representation (LRR) and random walk graph regularized NMF (RWNMFC) to accurately reveal the natural grouping of cells. Specifically, we find the lowest rank representation of single-cell samples by non-negative LRR to reduce the difficulty of analyzing high-dimensional samples and capture the global information of the samples. Meanwhile, by using random walk graph regularization (RWGR) and NMF, RWNMFC captures manifold structure and cluster information before generating a cluster allocation matrix. The cluster assignment matrix contains cluster labels, which can be used directly to get the clustering results. The performance of NLRRC is validated on simulated and real single-cell datasets. The results of the experiments illustrate that NLRRC has a significant advantage in single-cell type identification.

KGLRR: A low-rank representation K-means with graph regularization constraint method for Single-cell type identification.

Single-cell RNA sequencing technology provides a tremendous opportunity for studying disease mechanisms at the single-cell level. Cell type identification is a key step in the research of disease mechanisms. Many clustering algorithms have been proposed to identify cell types. Most clustering algorithms perform similarity calculation before cell clustering. Because clustering and similarity calculation are independent, a low-rank matrix obtained only by similarity calculation may be unable to fully reveal the patterns in single-cell data. In this study, to capture accurate single-cell clustering information, we propose a novel method based on a low-rank representation model, called KGLRR, that combines the low-rank representation approach with K-means clustering. The cluster centroid is updated as the cell dimension decreases to better from new clusters and improve the quality of clustering information. In addition, the low-rank representation model ignores local geometric information, so the graph regularization constraint is introduced. KGLRR is tested on both simulated and real single-cell datasets to validate the effectiveness of the new method. The experimental results show that KGLRR is more robust and accurate in cell type identification than other advanced algorithms.

Blood glucose mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers.

OBJECT: To explore the effects of occupational aluminum exposure on workers' cognitive function and blood glucose concentration, and to analyze whether blood glucose concentration can mediate the cognitive changes caused by aluminum. METHOD: Our study recruited 375 workers from an aluminum factory in northern China. We collected the fasting elbow venous blood of the workers, measured their fasting blood glucose concentration (FBG), and used ICP-MS to determine plasma aluminum concentration (P-Al) as an indicator of internal exposure. The Montreal Cognitive Assessment (MoCA), was used to assess the cognitive function of workers. Generalized linear model was used to analyze the association of P-Al with cognitive function and blood glucose concentration, and the restricted cubic spline model was used to fit the dose-response relationship. We also conducted a mediation effect analysis. RESULT: We observed the dose-response relationship, that is, as the P-Al increased, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased, and the blood glucose concentration increased. For every e-fold increase in P-Al, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased by 0.328 points, 0.120 points, 0.059 points, 0.060 points, and 0.083 points, respectively, and FBG rose by 0.109 mmol/L. FBG has a significant mediating effect between P-Al and sum of MoCA (P for mediator=0.042), and it could explain 10.7% of the effect of cognitive level related to P-Al. CONCLUSION: Occupational aluminum exposure negatively affected the cognitive function of workers and positively affected FBG. FBG may partially explain the impact of occupational aluminum exposure on workers' cognitive function.

Nitric oxide impairs spatial learning and memory in a rat model of Alzheimer's disease via disturbance of glutamate response in the hippocampal dentate gyrus during spatial learning.

Nitric oxide (NO)-dependent pathways may play a significant role in the decline of synaptic and cognitive functions in Alzheimer's disease (AD). However, whether NO in the hippocampal dentate gyrus (DG) is involved in the spatial learning and memory impairments of AD by affecting the glutamate (Glu) response during these processes is not well-understood. Here, we prepared an AD rat model by long-term i.p. of D-galactose into ovariectomized rats, and then the effects of L-NMMA (a NO synthase inhibitor) on Glu concentration and amplitude of field excitatory postsynaptic potential (fEPSP) were measured in the DG region during the Morris water maze (MWM) test in freely-moving rats. During the MWM test, compared with the sham group, the escape latency was increased in the place navigation trial, and the percentage of time spent in target quadrant and the number of platform crossings were decreased in the spatial probe trial, in addition, the increase of fEPSP amplitude in the DG was significantly attenuated in AD group rats. L-NMMA significantly attenuated the spatial learning and memory impairment in AD rats, and reversed the inhibitory effect of AD on increase of fEPSP amplitude in the DG during the MWM test. In sham group rats, the Glu level in the DG increased significantly during the MWM test, and this response was markedly enhanced in AD rats. Furthermore, the response of Glu in the DG during spatial learning was recovered by microinjection of L-NMMA into the DG. Our results suggest that NO in the DG impairs spatial learning and memory and related synaptic plasticity in AD rats, by disturbing the Glu response during spatial learning.

An Assessment of Social Media Usage Patterns and Social Capital: Empirical Evidence From the Agricultural Systems of China.

This research offers a theoretical model to measure the impact of social media usage on social capital in the agricultural system of China. Furthermore, this research also investigates the relationship between agricultural policies related to entrepreneurship training and social media usage. A total of 589 questionnaires were distributed in the training courses of Fujian Agricultural Vocational Technology College, and, Fuzhou, Quanzhou, Jianning, and Liancheng counties and cities in Fujian during winter and summer vacations to target new vocational farmers. The results show that social use, hedonic use, and cognitive use of social media significantly impacted both bridging and bonding social capital. Furthermore, the results of the study suggest that entrepreneurs who have participated in the training have significantly higher levels of social use and cognitive use than those who have not been trained. The findings of this paper have implications for the digital transformation by agricultural entrepreneurs in recognition of the role of sustainable education and learning in entrepreneurial activities and the utilization of social and cognitive functions of social media to acquire and accumulate social capital and provide support for sustainable agriculture and rural development. Furthermore, the concepts of sustainability-driven agriculture in the digital transformational framework were also studied and it was indicated that transformed agriculture can effectively deal with the present challenges.

Prevalence and Clinical Characteristics of Fabry Disease in Chinese Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The prevalence of Fabry disease (FD) in Chinese patients with hypertrophic cardiomyopathy (HCM) is unclear. We aimed to evaluate the prevalence, clinical characteristics, and outcomes of FD in Chinese patients with HCM. METHODS: Of 217 patients with HCM, FD probands were screened by next-generation sequencing at Fuwai Hospital. Medical data from α-galactosidase A activity, electrocardiography, echocardiography, coronary angiography, cardiac magnetic resonance, pathological examination, and follow up was analyzed. RESULTS: Two FD probands were observed (0.93% of patients with HCM), both of which were diagnosed with symptomatic obstructive HCM at 49 years of age. One proband had a GLA mutation (c.887T>C [p.M296T]) with a late-onset cardiac variant, which was characterized by dual ventricular hypertrophy and conduction disease with a permanent pacemaker. The other patient had a GLA mutation (c.758T>C [p.I253T]) with a classic phenotype and dual ventricular hypertrophy, atrioventricular block, renal failure, and recurrent cerebral infarction. Both probands had late gadolinium enhancement mainly in the basal segment of the inferolateral wall. Follow up revealed no exertional symptoms or outflow obstruction after surgical septal myectomy in the two probands, and stable renal function was observed after 6 months of migalastat therapy in the later one. A family study revealed six female carriers and three sudden cardiac deaths. CONCLUSIONS: FD is not uncommon in Chinese patients with HCM. Multiple organic involvement, dual ventricular hypertrophy, and conduction disease provide clinical clues for suspected FD, and early genetic screening is necessary. Surgical septal myectomy and migalastat improve the long-term prognosis of patients with FD.

Understanding the Impact of Social Capital on Entrepreneurship Performance: The Moderation Effects of Opportunity Recognition and Operational Competency.

Social capital, which is derived from psychological research, has an important value in the construction of network relationships in enterprises. It influences the direction and tendency of network connections in start-up enterprises and has gradually become an important factor in the study of entrepreneurship by scholars. However, the relationship between this and the effectiveness of innovation is unclear. In this study, the social capital is divided into bonding social capital and bridging social capital, and specific data of agricultural entrepreneurs are collected through questionnaire surveys. The results show that both bonding and bridging social capital have a significant positive effect on agricultural entrepreneurship performance. The entrepreneurial capacity of agricultural entrepreneurs regulates the relationship between social capital and creative performance. In the relationship between integrated social capital and creative performance, operational competency plays a positive role and opportunity recognition plays a negative role. On the other hand, in the relationship between bridging social capital and creative performance, the opportunity recognition plays a positive role and the operational competency plays a negative role. Finally, based on the above findings, this study proposes theoretical and practical implications and suggestions for follow-up research.

Longitudinal study of the effects of occupational aluminium exposure on workers' cognition.

OBJECTIVE: To explore the effects of occupational aluminium(Al) exposure on workers' cognition through a longitudinal study. METHODS: The study population consisted of 276 workers in an Al factory. In 2014, we used inductively coupled plasma mass spectrometry (ICP-MS) to determine the plasma aluminium (P-Al) concentration of the workers, and a combined questionnaire to test the workers' cognitive function. Followed-up in 2016, the workers were tested again for cognitive function. Generalized linear regression was used to assess the association between P-Al concentration and cognitive scores, and multivariable logistic regression was used to assess the risk of cognitive decline caused by Al exposure. RESULTS: Generalized linear regression results showed that a non-significant association was found between the P-Al concentration and cognitive test scores (P > 0.05) in 2014. Two years later, each 10-fold increase in P-Al concentration was inversely associated with the score of Mini-Mental state examination (MMSE) (ß: -0.53, 95% CI: -0.86, -0.20) and Fuld object memory evaluation (FOME) (ß: -0.93, 95% CI: -1.62, -0.24). Each 10-fold increase in P-Al concentration was inversely associated with MMSE2016-2014 (ß: -0.38, 95% CI: -0.74, -0.01) and FOME2016-2014 (ß: -1.20, 95% CI: -1.95, -0.45). There was a statistically significant difference in the average annual rate of change of MMSE and FOME with the tertile of P-Al concentration increase (P < 0.05). The multivariable logistic regression results showed that as the P-Al concentration increased, the risk of a FOME score decline increased (Ptrend = 0.009). CONCLUSIONS: Continuous occupational Al exposure can damage workers' overall cognitive ability, especially episodic memory function.

Cross-sectional study based on occupational aluminium exposure population.

To evaluate the different characteristics of cognitive impairment caused by occupational aluminium exposure at different ages, we surveyed 1660 workers in Shanxi Aluminium Plant, China, and assessed their cognitive function and plasma aluminium concentration. In multiple linear regression, the scores of the digit-span test (DST) and digit-span backward test (DSBT) were negatively correlated with plasma aluminium concentration when concentration reached 34.52 µg/L in younger group (＜40 years), while in the middle-aged group (≥40 years) only found when concentration reached 42.25 µg/L (ß<0, P < 0.05). In logistic regression, when plasma aluminum concentration reached 42.25µg/L, odds ratios (95 % confidence interval) were 1.695 (1.062-2.705) and 3.270 (1.615-6.620) for DST, 7.644 (3.846-15.192) and 15.308 (4.180-56.059) for DSBT in middle-aged group and younger group, respectively. These results showed that aluminium exposures were associated with cognitive impairment among aluminium-exposed workers, particularly for young workers who were more susceptible.

Forkhead Box Q1 Is Critical to Angiogenesis and Macrophage Recruitment of Colorectal Cancer.

Angiogenesis and the tumor microenvironment (TME) play important roles in tumorigenesis. Forkhead box Q1 (FOXQ1) is a well-established oncogene in multiple tumors, including colorectal cancer (CRC); however, whether FOXQ1 contributes to angiogenesis and TME modification in CRC remains largely uncharacterized. Here, we demonstrate an essential role of FOXQ1-induced angiogenesis and macrophage recruitment in CRC that is related to its ability to promote the migration of endothelial cells and macrophages through activation of the EGF/PDGF pathway and the Twist1/CCL2 axis. We also provide evidence showing that the clinical significance between FOXQ1, Twist1, CCL2, and macrophage infiltration is associated with reduced 8-year survival in CRC patients. Our findings suggest FOXQ1 plays critical roles in the malignancy and progression of CRC, Therefore, FOXQ1 may serve as a therapeutic target for inhibiting angiogenesis and reducing macrophage recruitment in CRC.

Apparent mineralocorticoid excess caused by novel compound heterozygous mutations in HSD11B2 and characterized by early-onset hypertension and hypokalemia.

PURPOSE: Apparent mineralocorticoid excess (AME) is an ultrarare autosomal recessive disorder resulting from deficiency of 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) caused by mutations in HSD11B2. The purpose of this study was to identify novel compound heterozygous HSD11B2 mutations in a Chinese pedigree with AME and conduct a systematic review evaluating the AME clinical features associated with HSD11B2 mutations. METHODS: Next-generation sequencing was performed in the proband, and Sanger sequencing was used to identify candidate variants in family members, 100 hypertensives, and 100 healthy controls. A predicted structure of 11ßHSD2 was constructed by in silico modeling. A systematic review was used to identify cases of HSD11B2-related AME. Data for genotyping and clinical characterizations and complications were extracted. RESULTS: Next-generation sequencing showed novel compound heterozygous mutations (c.343_348del and c.1099_1101del) in the proband with early-onset hypertension and hypokalemia. Sanger sequencing verified the monoallelic form of the same mutations in five other relatives but not in 100 hypertensives or 100 healthy subjects. In silico structural modeling showed that compound mutations may simultaneously perturb the substrate and coenzyme binding pocket. A systematic review of 101 AME patients with 54 HSD11B2 mutations revealed early-onset hypertension, hypokalemia and homozygous mutations as common features. The homozygous HSD11B2 mutations correlated with low birth weight (r = 0.285, P = 0.02). CONCLUSIONS: We report novel compound heterozygous HSD11B2 mutations in a Chinese teenager with early-onset hypertension, and enriched genotypic and phenotypic spectrums in AME. Genetic testing helps early diagnosis and treatment for AME patients, which may avoid target organ damage.

Whole exome sequencing identified a pathogenic nonsense mutation in LMNA in a family with a progressive cardiac conduction defect: A case report.

Progressive cardiac conduction defect (PCCD) is an inherited autosomal dominant cardiac disorder characterized by an age­dependent cardiac electrical conduction block. Several genes have been associated with the genetic pathogenesis of PCCD. The present study aimed to identify the causal mutation of PCCD and to investigate the association between genotype and phenotype in a Chinese family with PCCD. A total of 39 family members were included in the present study. All subjects participated in physical, biochemical, electrocardiography and echocardiography examinations. Whole­exome sequencing was performed for four individuals from the same generation, including three patients with PCCD and one normal control with no cardiovascular disease. Sanger sequencing and in silico analysis were used to identify the causal mutation. Whole­exome sequencing and variant identification revealed a candidate nonsense mutation (c.1443C>A, p.Tyr481*) in lamin A/C (LMNA). The mutation was identified in seven patients (including the proband) and two asymptomatic mutation carriers, but it was not detected in 100 control subjects of matched ancestry. Clinical examinations identified typical symptoms in patients with PCCD, including bradycardia and various types of conduction defect, and excluded other phenotypes related to the LMNA mutation. The genotype and phenotype were co­associated among all participants. In the present study, the c.1443C>A mutation in the LMNA gene was identified as a potential cause of PCCD. In silico analysis predicted that the identified mutation was damaging through its effect on the lamin tail domain of LMNA. From the present study, it could be suggested that genetic screening and family counseling, early pacemaker implantation or a sudden death in the family may be essential for risk stratification and treatment of patients with PCCD.

Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension.

BACKGROUND: Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS: Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS: Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS: This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.

Tuberculosis in Takayasu arteritis: a retrospective study in 1105 Chinese patients.

BACKGROUND: Tuberculosis (TB) infection has been reported to have a possible relationship with the occurrence and clinical course of Takayasu arteritis (TA). We aimed to describe the characteristics of TB in a large population of TA patients. METHODS: We included a total of 1105 patients with TA, who were hospitalized between January 1992 and December 2017. Comparisons of clinical features were made according to the presence of TB. RESULTS: Among the 1105 patients, 109 (9.9%) had TB, including 53 patients (48.6%) diagnosed with TB before the onset of TA, 23 (21.1%) with a concurrent diagnosis of TB and TA, and 24 patients (22.0%) who developed TB after TA. Pulmonary TB was the most frequently identified (97 patients, 89.0%). Patients with TB had more frequent involvement of the pulmonary artery and experienced more chest discomfort and constitutional symptoms but had less interventional treatment. Demographic characteristics, comorbid diseases, and use of steroids were similar between patients with and without TB. CONCLUSIONS: The proportion of Chinese TA patients with TB was not low, and about half of the patients had TB before TA. Pulmonary TB was the most common. Pulmonary artery involvement and pulmonary hypertension was more frequent in TA patients with TB.

Aortic Aneurysm in Takayasu Arteritis.

BACKGROUND: Aortic aneurysm (AA) is a severe complication of Takayasu arteritis (TA). This study aimed to evaluate the prevalence, clinical and imaging features, management and long-term outcomes of AA in patients with TA. MATERIALS AND METHODS: A retrospective study was performed of TA patients with AA admitted to Fuwai Hospital from 1996-2015. Baseline clinical data and follow-up data of TA patients with AA were collected and analyzed. RESULTS: Thirty-nine (4.2%) of 934 patients with TA were identified with AA that was related to vasculitis. The mean age at disease onset was 31 ± 10 years, with a female-to-male ratio of 1.79:1. The ascending aorta was the most common site of the aneurysmal lesion (18, 33.3%), and the most frequent manifestations associated with AA were chest tightness (12, 30.8%) and shortness of breath (12, 30.8%), which were usually concomitant with aortic valve insufficiency. Involvement of multiple sites in AA was found in 8 patients (20.5%), and multiple AAs were found in 5 patients (12.8%). No significant difference was observed in clinical and imaging findings between sexes. Of 25 patients (64.1%) with a median 72-month follow-up, 1 patient suffered from heart failure owing to perivalvular leakage, and 1 patient died, possibly related to severe complications of the operation. CONCLUSIONS: The prevalence of AA is relatively low in Chinese patients with TA. AA seems to develop more frequently in male patients with TA. Management should consider location and size of AA, complexity of vessel lesions and disease status. Long-term follow-up is indispensable.

Left Ventricular Noncompaction in Older Patients.

BACKGROUND: Information on left ventricular noncompaction (LVNC) in older people is sparse. This study aimed to investigate the clinical profile of LVNC in an older cohort. MATERIALS AND METHODS: Between August 2007 and September 2015, older patients (age ≥ 60 years) who were diagnosed with LVNC using cardiovascular magnetic resonance were prospectively enrolled at our hospital. RESULTS: A total of 35 patients (male, 80%; mean age, 65 ± 5 years) were prospectively included in this study. LVNC was not detected in 18 patients (51%) at the initial echocardiographic evaluation. Of the 21 patients who received coronary imaging, 8 patients (38%) had coronary artery disease. Left ventricular (LV) dysfunction and dilation were detected in 31 patients (89%) and 30 patients (86%), respectively. Nine patients (26%) died during a follow-up period of 2.9 ± 2.3 years. Cox analysis showed that patients with syncope (hazard ratio [HR] = 20.51; 95% CI: 1.70-246.60; P = 0.02), increased LV end-diastolic diameter (HR = 1.12; 95% CI: 1.01-1.24; P = 0.03), decreased LV ejection fraction (HR = 0.87; 95% CI: 0.77-0.98; P = 0.02) and the presence of late gadolinium enhancement on cardiovascular magnetic resonance (HR = 8.9; 95% CI: 1.07-74.08; P = 0.04) had a higher risk for death. CONCLUSIONS: The diagnosis of LVNC is easily missed at echocardiographic assessment in older patients. Coronary artery disease is a common concomitant disorder in these patients. Older patients with LVNC have a high risk for mortality. Syncope, LV dilation, systolic dysfunction and late gadolinium enhancement are related to adverse outcomes in older patients.

A novel PRKAG2 mutation in a Chinese family with cardiac hypertrophy and ventricular pre-excitation.

PRKAG2 syndrome is a rare autosomal dominant inherited disorder that is characterized by cardiac hypertrophy, ventricular pre-excitation and conduction system abnormalities. There is little knowledge in cardiovascular magnetic resonance (CMR) characteristics of PRKAG2 cardiomyopathy. This study investigated the genetic defect in a three-generation Chinese family with cardiac hypertrophy and ventricular pre-excitation using whole-exome sequencing. A novel missense mutation, c.1006 G > T (p.V336L), was identified in PRKAG2. This mutation had not been identified in the ExAC database, and the prediction result of MutationTaster indicated a deleterious effect. Furthermore, it cosegregated with the disease in the present family and was absent in unrelated 300 healthy controls. cDNA analysis did not detect any splicing defects, although the variant occurred in the first base of exon 9. CMR evaluation in five affected members showed diffuse hypertrophy in a concentric pattern, with markedly increased left ventricular mass above age and gender limits (median 151.3 g/m2, range 108.4-233.4 g/m2). Two patients in progressive stage and one patient with sudden cardiac death exhibited extensive subendocardial late gadolinium enhancement. In conclusion, molecular screening for PRKAG2 mutations should be considered in patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation. CMR offers promising advantages for evaluation of PRKAG2 cardiomyopathy.

Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy.

The aim of the present study was to determine the genetic basis of a multi-generational family with late-onset (LO) Fuchs corneal dystrophy (FCD). Five FCD causal genes [solute carrier family 4, sodium borate transporter, member 11 (SLC4A11), zinc finger E-box binding homeobox 1 (ZEB1), lipoxygenase homology domains 1 (LOXHD1), collagen, type VIII, alpha 2 (COL8A2) and transcription factor 4 (TCF4)], previously reported to be implicated in the pathogenesis of FCD, were screened. A total of 27 variants [including 22 known single nucleotide polymorphisms (SNPs) from the Single Nucleotide Polymorphism Database (dbSNP) and 5 variants absent from dbSNP] were detected in this FCD pedigree across the SLC4A11, ZEB1, LOXHD1 and COL8A2 genes as follows: i) 22 known SNPs from dbSNP, including 3 coding (p.R161R, p.S213S and p.T833T) and 11 non-coding variants of SLC4A11, 2 intronic SNPs of ZEB1 from dbSNP (rs220057 and rs220060), 1 intronic SNP of LOXHD1 from dbSNP (rs16939650), and 5 SNPs of COL8A2 from dbSNP (p.A35A, p.R155Q, p.L335L, p.G495G and p.T502M); and ii) 5 variants that have not been previously reported in FCD patients and that are absent from dbSNP were identified across the ZEB1 and LOXHD1 genes; these included 3 continuous indels located at the junction of the 5'-UTR and the adjacent exon 1 of ZEB1 [Indel 1 (c.-86_-53delins gggaggggtggaggcggaggggtGGGGGGGAAGG); Indel 2 (c.-52_-46delinsGGGAGGG); and Indel 3 (c.-45_-42delinsAGGG)], and 2 intronic variants of LOXHD1 (c.5332-126C>T and c.1809+155G>A). Apart from one intronic SNP of SLC4A11 from dbSNP (rs372201212), the pathologic consequence of which is uncertain, and 2 intron variants of LOXHD1 (c.5332-126C>T and c.1809+155G>A); the variants likely represent examples of de novo mutations. Neither of the other 24 variants provided strong evidence of pathogenesis in this FCD pedigree. An analysis of 7 SNPs in TCF4 from dbSNP, which have been associated with LO FCD in different populations, revealed that these 7 SNPs were not associated with FCD in this specific pedigree. A genome­wide linkage scan to search for linkage to one of the previously described FCD loci or to identify a novel locus for FCD will need to be performed in this FCD pedigree. Our observation, nevertheless, expands the knowledge of the genetic status of patients with FCD.