Compound heterozygous NDUFS1 variants identified in a Chinese pedigree affected with mitochondrial respiratory chain complex I deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing.@*METHODS@#Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing.@*RESULTS@#Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis.@*CONCLUSION@#Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.

The use of in vivo cryotechnique in combination with electrocardiograph to study cardiac microcirculation in living mouse / 中国医师杂志

Objective The use of in vivo cryotechnique (IVCT) in combination with electrocardiograph (ECG) to study cardiac microcirculation under different hemodynamic conditions in living mouse.Methods Living mouse heart monitored by electrocardiograph was suffered from IVCT and freezing substitution under normal blood flow,myocardial ischemia or cardiac arrest conditions.Hematoxylin eosin (HE)staining,Schiff's staining and immunofluorescence staining for serum albumin,immunoglobulin were utilized on continuous paraffin sections,respectively.Confocal microscopy and statistical analyses were used.Results Comparing with normal hemodynamics,microvascular red cell volume reduction,morphology changed,myocardial cell glycogen loss,serum albumin ectopic distribution to myocardial cytoplasm,T tubular network failure and spacing width were happened in myocardial iscbemia condition; different shapes of red blood cells,myocardial cells glycogen deficiency,T tubular network failure and interval narrowing were found under cardiac arrest conditions.Conclusions Cardiac microcirculation,pathological changes of myocyte and its surrounding microenviroument in living mouse heart can be immediately captured in situ by the application of IVCT and ECG.

Value of four combined views of two-dimensional echocardiography in prenatal screening for fetal congenital heart disease / 中华围产医学杂志

ObjectiveTo investigate the value of combined four-chamber view,left and right ventricular outflow tract view and three-vessel view of two-dimensional echocardiography (2DE) in prenatal screening for fetal congenital heart disease (CHD). MethodsFour combined views of 2DE were used to detect fetal hearts in 2419 fetuses at 21～ 25 gestational weeks.The echocardiograms were performed on all 2382 live-birth infants.Chi-square test was applied for statistical analysis.Sensitivity,specificity,positive predict value and negative predict value were calculated. Results The prevalence of fetal CHD was 11.62％ (281/2419).Among the 281 CHD fetuses,87.18％ were simple CHD (n=245) and 12.82％ were complex CHD (n=36).No difference was found in the positive rate of fetal CHD between the high-risk group and non-high-risk group [13.60％(34/250) vs 11.39％(247/2169),x2=1.069,P＜0.05].Thirty-six cases of CHD could be detected by the four combined views in prenatal screening with the sensitivity,specificity,positive and negative predictive value of 12.8％,99.8％,90.0％ and 89.7％,respectively.However,the diagnostic sensitivity of four combined views for simple CHD was 2.9％(7/245) and 80.6％(29/36) for complex CHD.The prevalence of neonatal CHD was 10.58％ (252/2382),including 241 with simple CHD and 11 complex ones. ConclusionsFour combined views of 2DE for prenatal screening is less sensitive in detecting simple CHD than complex CHD.Most of the complex CHD could be diagnosed by four combined views of 2DE before birth,but the misdiagnosis rate is high in simple CHD.The echocardiograms performed on newborns might make up for the lack.