Genotype and clinical phenotype analysis of a five-generation Ningxia family with autosomal dominant retinitis pigmentosa pedigree / 中华实验眼科杂志

Objective:To identify the pathogenic mutation in a five-generation Ningxia family with autosomal dominant retinitis pigmentsoa (adRP) and to analyze its associated clinical phenotype.Methods:One adRP pedigree was recruited for this study.All the patients and family members received complete ophthalmic examinations.DNA was abstracted from peripheral blood of three patients, one normal family member and 300 normal controls.Using whole exome sequencing (WES) chip and bioinformatics analysis to screen the candidate disease-causing mutations.PCR and direct sequencing were used to confirm the disease-causing mutations.Genotype-phenotype correlation was also analyzed.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of People's Hospital of Ningxia Hui Autonomous Region (No.20160204).Results:PRPF31 c. C1048T (p.Q350X) nonsense mutation was identified as the disease-causing mutation for this family by WES chip, PCR and direct sequencing.This family demonstrated early onset of the disease by presenting nyctalopia from 5 to 6 years, performed rapid disease progression, severely impaired visual function and posterior subcapsular cataract.The fundus presentations and electroretinogram (ERG) results showed typical RP progressions. Conclusions:PRPF31 c. C1048T (p.Q350X) nonsense mutation is the disease-causing mutation of this family.This mutation is first reported in Chinese with distinct phenotypes in the present family, including early onset of the disease, rapid disease progression, severely impaired visual function and posterior subcapsular cataract.

Myocardial Contrast Echocardiography Evaluation of Tirofiban for the Myocardial Reperfusion of NSTEMI Patients Underwent PCI Treatment / 现代生物医学进展

Objective:To explore the improvement effect of tirofiban on the myocardial reperfusion of non-ST segmant elevated myocardial infarction (NSTEMI) patients underwent percutaneous coronary intervention (PCI) treatment.Methods:78 NSTEMI patients underwent PCI in our hospital from April 2012 to April 2015 were selected and divided into the observation group (n=38) and the control group (n=40) according to different drugs.Patients in the control group were given asprin,clopidogrel and heparin,while patients in the observation group were additionally given tirofiban.Then the myocardial contrast echocardiography (MCE) was taken to evluate the myocardial reperfusion.Results:No statistical difference was found in the levels of A,β,A β,CK-MB and cTnⅠ before PCI between 2 groups.The levels of β,A β of observation group were obviously higher,CK-MB and cTnⅠ were obviously lower than those of the control group(P＜0.05).The MACE rate of observation group was 2.63％,which was 5.00％ in the control group,no significant difference was between two groups (P＞0.05).Conclusion:Tirofiban could obviously improve the myocardial reperfusion of NSTEMI patients underwent PCI with high safety.

Rapid identification of pathogenic mutations in sporadic hereditary retinal dystrophies using targeted next-generation sequencing / 中华实验眼科杂志

Background Hereditary retinal diseases (HRDs) are a group of retinal degenerative diseases with significant genetic and clinical heterogeneities.Traditional techniques are challenging for detection of pathogenic mutations.Objective This study was to identify the diseasing-causal genes in 20 Chinese families with a variety of HRDs.Methods Family histories and ophthalmic examinations were obtained from all participants in 20 sporadic families.Targeted sequence capture array technique with next-generation sequencing (NGS) was performed to detect pathogenic mutations in 232 identified genes associated with HRDs.Variants detected by NGS were filtered by bioinformatic analysis HRDs.Genotype-phenotype correlation was also assessed.Results We identified 11 patients with pathogenic mutations,including 8 compound heterozygous mutations and 3 homozygous mutations,which were not yet reported.These findings showed genetic diagnoses in 11 of 20 patients,with the positive rate of 55％.Among them,6 patients were autosomal recessive inheritance and 5 were unspecific.Identification of different mutations and divergent phenotypes revealed 5 patients were affected with cone-rod dystrophy,3 patients with Leber congenital amaurosis,1 patient with congenital stationary night blindness,1 patient with Best vitelliform macular dystrophy and 1 patient with Stargardt disease.Conclusions Targeted NGS is an effective approach for the genetic diagnoses of HRDs.These findings provide insights into understanding the genotype-phenotype correlations in HRDs.

Detection of disease-causing gene in a Hui congential cataract pedigree by exon combined target region capture sequencing chip / 中华实验眼科杂志

Background Congenital cataract is an important cause of blindness and amblyopia in children,and about 50％ of congenital cataract is hereditary.Objective The aim of this study was to determine the diseasecausing gene of one Hui congenital cataract pedigree by using exon combined target region capture sequencing chip of eye diseases.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and followed Declaration of Helsinki.One Hui congenital cataract pedigree was recruited in Ningxia Eye Hospital in 2011.All the disease history of the members in this family were collected and recorded,and the eye examinations were performed.The peripheral blood specimens were collected from family members and 300 healthy individuals for the extraction of DNA.Exon combined target region capture sequencing chip of eye diseases was used to screen the candidate diseasecausing mutations,then PCR and direct sequencing were used to confirm the disease-causing mutations.Results This H ui family included 61 members of 6 generations,and 18 patients were diagnosed in serial 5 passages,conforming to autosomal dominant inheritance pattern.Among 18 cataract patients,7 individuals were associated with nystagmus and strabismus,and 4 patients had high myopia.Eight candidate pathogenetic mutations were detected by exon combined target region capture sequencing chip of eye diseases and bioinformatics method,with 5 mutations in noncoding regions and 3 in coding regions.The mutation P24T of CYRGD gene was confirmed as pathogenic mutation of this pedigree by using PCR and direct sequencing methods.These mutations co-segregated with affected members of the family,and the mutations were not found in the unaffected family members and 300 unrelated controls.Conclusions P24T of CYRGD gene mutation is confirmed as pathogenic mutation of this pedigree.Exon combined target region capture sequencing chip provides a new approach to detect disease-causing mutations of congenital cataract with diversity clinical phenotypes.