Genetic analysis of a patient with Alport syndrome due to compound heterozygous variants of COL4A4 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome.@*METHODS@#A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family.@*RESULTS@#The main clinical manifestations of the patient included hematuria, proteinuria, and impaired hearing. Audiometric testing suggested symmetrical cochlear sensory neural hearing loss on both sides. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. Genetic testing revealed that the patient has harbored compound heterozygous variants of the COL4A4 gene, namely c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp), which were respectively inherited from her father and mother. Neither variant has been reported before, and were predicted to be pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#The c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp) compound heterozygous variants of the COL4A4 gene probably underlay the Alport syndrome in this patient. Above finding has enriched the mutational spectrum of the COL4A4 gene.

Selective Aberrant Functional–Structural Coupling of Multiscale Brain Networks in Subcortical Vascular Mild Cognitive Impairment / 神经科学通报·英文版

Subcortical vascular mild cognitive impairment (svMCI) is a common prodromal stage of vascular dementia. Although mounting evidence has suggested abnormalities in several single brain network metrics, few studies have explored the consistency between functional and structural connectivity networks in svMCI. Here, we constructed such networks using resting-state fMRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls. The functional networks were then parcellated into topological modules, corresponding to several well-defined functional domains. The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level (whole brain and modular level). We found no significant intergroup differences in the functional–structural coupling within the whole brain; however, there was significantly increased functional–structural coupling within the dorsal attention module and decreased functional–structural coupling within the ventral attention module in the svMCI group. In addition, the svMCI patients demonstrated decreased intramodular connectivity strength in the visual, somatomotor, and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network, mainly linking the visual, somatomotor, dorsal attention, ventral attention, and frontoparietal control modules. There was no significant correlation between the altered module-level functional–structural coupling and cognitive performance in patients with svMCI. These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.

Associations between vitamin D deficiency and nonalcoholic fatty liver disease / 中华消化杂志

Objective To explore the association between vitamin D deficiency and nonalcoholic fatty liver disease (NAFLD).Methods From April to June 2013,104 outpatients met NAFLD diagnostic criteria were enrolled.At the same period,98 age and gender matched healthy individuals were enrolled as control.The clinical data were collected through questionnaire,physical examination and lab tests.The severity of hepatic steatosis was dertermined with upper abdominal ultrasound examination.The serum concentration of 25 (OH )D was detected by radio-immunology.The association between vitamin D deficiency and NAFLD was analyzed with two independent sampling t analysis,chi-square test,analysis of variance (ANOVA)and Logistic regression analysis.Results The clinical indexes including body mass index (BMI ), abdominal circumference, blood pressure, aspartate aminotransferase, alanine aminotransferase,glutamyl ranspeptidase,lactate dehydrogenase,uric acid,triglyceride,overall cholesterol, lower density lipoprotein cholesterol and fasting blood glucose of NAFLD group were higher than those of the healthy control group,and the differences were statistically significant (all P 0.05).The results of stratification analysis in age and BMI indicated that the rate of 25 (OH )D deficiency (<37.5 nmol/L)in NAFLD patients aged less than 30 was higher than that of healthy control group (χ2 =6.679, OR = 13.71,P = 0.025 );the rate of 25 (OH)D deficiency in NAFLD patients with BMI≤25 kg/m2 was higher than that of healthy control group (χ2 = 3.734,OR = 4.97,P < 0.01).Among BMI≤25 kg/m2 group,after the adjustment of age,gender and metabolic syndrome,the results of multiple group Logistic regression analysis indicated that serum 25(OH)D concentration was negatively correlated to NAFLD (OR= 1 .16,95 % CI :1 .03 to 1 .30,P = 0.032).Conclusion Vitamin D deficiency might be a risk factor in pathogenesis of NAFLD patients with age less than 30 year old and BMI ≤25 kg/m2 .

Comparative study on left ventricular systolic function in patients with implanted dual-chamber(DDD) mode cardiac pace-makers using two-dimensional and real-time three-dimensional echocardiography / 中国医师杂志

Objective To assess the left ventricular systolic function (LVSF) in patients with implanted dual-chamber(DDD) mode cardiac pacemakers using Two-dimensional Echocardiography (2DE),Real-time Tri-plane Echocardiography (RT-3PE)and Full-volume Three Dimensional Echocardiography (FV-3DE).Methods A total of 30 patients with DDD mode cardiac pacemaker were ex-amined by 2DE, RT-3PE and FV-3DE separately.Left ventricle end diastolic volume (LVEDV), left ventricle end systolic volume (LVESV), and ejection fraction (EF) were measured and compared within the three methods above .Results The measurement of EF with patients of post-operation was higher than the patients of pre-operation.The measurements of EF with 2DE were higher than RT-3PE.The measurements of LVEDV , LVESV and SV with 2DE and RT-3PE were lower than FV-3DE, and EF was higher .There were statistically significant differences in above measurements ( P 0.05).Conclusions Implanting DDD mode cardiac pace-maker can evaluate LVSF of patients obviously .FV-3DE can evaluate LVSF in patients with DDD mode cardiac pacemaker accurately . The LVEDV, LVESV and SV are underestimated by 2DE and RT-3PE, and EF is overestimated by 2DE and RT-3PE.