scholarly journals Ocular phenotype and genetical analysis in patients with retinopathy of prematurity

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Tianchang Tao ◽  
Xianfen Meng ◽  
Ningda Xu ◽  
Jiarui Li ◽  
Yong Cheng ◽  
...  
Keyword(s):  
Retinopathy Of Prematurity ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Retinal Disease ◽  
Chinese Patients ◽  
Missense Mutations ◽  
Genetical Analysis ◽  
Pathogenic Genes ◽  
Clinical Presentations ◽  
Comprehensive Health

Abstract Background Retinopathy of prematurity (ROP) is a multifactorial retinal disease, involving both environmental and genetic factors; The purpose of this study is to evaluate the clinical presentations and genetic variants in Chinese patients with ROP. Methods A total of 36 patients diagnosed with ROP were enrolled in this study, their medical and ophthalmic histories were obtained, and comprehensive clinical examinations were performed. Genomic DNA was isolated from peripheral blood of ROP patients, polymerase chain reaction and direct sequencing of the associated pathogenic genes (FZD4, TSPAN12, and NDP) were performed. Results All patients exhibited the clinical manifestations of ROP. No mutations were detected in the TSPAN12 and NDP genes in all patients; Interestingly, three novel missense mutations were identified in the FZD4 gene (p.A2P, p.L79M, and p.Y378C) in four patients, for a detection rate of 11.1% (4/36). Conclusions This study expands the genotypic spectrum of FZD4 gene in ROP patients, and our findings underscore the importance of obtaining molecular analyses and comprehensive health screening for this retinal disease.

scholarly journals Association of the CD11b rs1143679 polymorphism with systemic lupus erythematosus in the Han Chinese population

2017 ◽  
Vol 46 (3) ◽  
pp. 1008-1014 ◽  
Author(s):  
Chunmei Li ◽  
Fengqing Tong ◽  
Yi Ma ◽  
Kai Qian ◽  
Junyu Zhang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Chinese Population ◽  
Direct Sequencing ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Systemic Lupus ◽  
Han Chinese Population

Objective To investigate the association of the CD11b single nucleotide polymorphism (SNP) rs1143679 with systemic lupus erythematosus (SLE) in Han Chinese patients, and to clarify this association with SLE clinical manifestations. Methods PCR–restriction fragment length polymorphism and direct sequencing of CD11b rs1143679 were conducted in 584 patients with SLE and 628 healthy controls in this case–control study to compare genotype and allele frequency distributions. Correlations between CD11b genotypes and clinical manifestations were also determined. Results The frequency of the CD11b rs1143679 GA genotype was 1.89% in Han Chinese patients with SLE, which was much lower than that of European and American populations, but close to the frequency observed in individuals from Hong Kong and Thailand. The CD11b rs1143679 GA genotype was also shown to confer susceptibility to SLE (odds ratio = 4.00, 95% confidence interval = 1.11–14.41). CD11b rs1143679 was found to be significantly associated with nephritis, but not with age of disease onset, arthritis, hematological involvement, or neural lesions. Conclusion CD11b rs1143679 appears to be associated with risk for SLE in the Han Chinese population, and may play an important role in the development of lupus nephritis.

scholarly journals Analysis of genetic and clinical characteristics of a Chinese Kallmann syndrome cohort with ANOS1 mutations

2017 ◽  
Vol 177 (4) ◽  
pp. 389-398 ◽  
Author(s):  
Min Nie ◽  
Hongli Xu ◽  
Rongrong Chen ◽  
Jiangfeng Mao ◽  
Xi Wang ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Clinical Presentation ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Kallmann Syndrome ◽  
Chinese Patients ◽  
Missense Mutations ◽  
The Novel ◽  
Novel Mutations ◽  
Functional Relevance

Objective To analyze ANOS1 gene mutations in a large Chinese Kallmann syndrome (KS) cohort and to characterize the clinical presentation of the disease in patients with ANOS1 mutations. Patients and methods Chinese patients with KS, including 187 sporadic and 23 pedigree cases were recruited. Patients’ ANOS1 gene sequences were analyzed by direct sequencing of PCR-amplified products. In silico analysis was used to assess functional relevance of newly identified missense mutations. Patients’ clinical characteristics were analyzed retrospectively. Result(s) Fifteen nonsynonymous rare ANOS1 variants were found in 13 out of 187 sporadic and 8 out of 23 familial IHH probands. Seven novel (C86F, C90Y, C151W, Y379X, c.1062 + 1G > A, Y579L fs 591X, R597X) and eight recurrent ANOS1 mutations (S38X, R257X, R262X, R423X, R424X, V560I, c.1843-1G > A, p.R631X) were identified. All the novel mutations were predicted to be pathogenic. The prevalence of cryptorchidism was high (38.1%) and occurred in patients with different kind of ANOS1 mutations, while the patients with the same mutation did not present with cryptorchidism uniformly. Conclusion(s) The prevalence of ANOS1 gene mutations is low in sporadic KS patients, but is much higher in familial KS patients. In the present study, we identify seven novel ANOS1 mutations, including two mutations in the CR domain, which are probably pathogenic. These mutations expand the ANOS1 mutation spectrum and provide a foundation for prenatal diagnosis and genetic counseling.

Abstract 535: Screening Mutations of MYBPC3 in 114 Unrelated Patients With Hypertrophic Cardiomyopathy Using Targeted Capture and Next-Generation Sequencing

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Xuxia Liu ◽  
Tengyong Jiang ◽  
Chunmei Piao ◽  
Tao Cai ◽  
Jie Du
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Low Cost ◽  
Nyha Class ◽  
Clinical Manifestations ◽  
Premature Termination Codon ◽  
Chinese Patients ◽  
Missense Mutations ◽  
Double Mutation ◽  
Targeted Resequencing ◽  
Mutation Group

Background and Purpose: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease and a major cause of sudden cardiac death. Mutations in the gene encoding the myosin binding protein C (MYBPC3) represent the cause of HCM in ~35% of all cases of HCM. However, genetic testing for MYBPC3 in clinic setting has been limited due to the cost and relatively time-consuming Sanger sequencing. Therefore, we developed a HCM gene diagnostic kit enabling ultra-low-cost candidate gene targeted resequencing in a large cohort. Methods: Clinical evaluations, electrocardiography and echocardiography data of all patients with HCM were collected in Anzhen Hospital, Beijing, from 2012 to 2013. Exomes were captured with MYBPC3-containing panel using biotinylatedoligo-probes and sequenced by Illumina HiSeq2000. Results: In a cohort of 114 patients with HCM, a total of 21 different mutations in the MYBPC3 gene, including 3 nonsense, 6 indels and 12 missense mutations, were identified from 29 patients. These patients were presented in a broad range of phenotypes with mean age of 36.6 ± 12.5 years at onset. Phenotype-genotype analyses showed that clinical manifestations (NYHA class 3~4) were more severe in the double-mutation group (n=3, 100%) as well as the premature termination codon (PTC) group (n=12, 50%), compared with the missense mutation group (n=14, 21.4%) (p=0.03). Interestingly, the p.Y842X mutation was detected in four unrelated cases (4/29, 13.79%) with severe phenotypes, such as syncope, arrhythmias, and history of receiving invasive therapies. Conclusions: We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients (~25.4%). We also confirmed that truncation mutations or double mutations in MYBPC3 could lead to relatively severe phenotypes, and propose that the p.Y842X mutation might be correlated with severe phenotypes in Chinese patients with HCM.

Identification of Genetic Defects Underlying FXII Deficiency in Four Unrelated Chinese Patients

2016 ◽  
Vol 135 (4) ◽  
pp. 238-240 ◽  
Author(s):  
Lihong Yang ◽  
Yingyu Wang ◽  
Jianpin Zhou ◽  
Xiaoli Cheng ◽  
Xiuping Hao ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Chinese Patients ◽  
Factor Xii ◽  
Missense Mutations ◽  
Molecular Defects ◽  
Coagulant Activity ◽  
Computer Based ◽  
Normal Human

Congenital factor XII (FXII) deficiency is a rare autosomal recessive disorder, characterized by a great variability in its clinical manifestations. In this study, we screened for mutations in the F12 gene of 4 unrelated patients with FXII coagulant activity <10% of that of normal human plasma. To investigate the molecular defects in these FXII-deficient patients, we performed FXII mutation screening. By sequencing all coding exons as well as flanking intronic regions of the F12 gene, 6 different mutations, including 3 missense mutations (Gly341Arg, Glu502Lys and Gly542 Ser), 1 insertion (7142insertC) and 2 deletions (5741-5742 delCA and 6753-6755delACA), were identified on the F12 gene. Three of them (Gly341Arg, 5741-5742delCA and 6753-6755delACA) are reported here for the first time. Computer-based algorithms predicted these missense mutations to be deleterious. This study has increased our knowledge of the mutational spectrum underlying FXII deficiency.

Genetic Features of Chinese Patients with Gitelman Syndrome: Sixteen Novel SLC12A3 Mutations Identified in a New Cohort

2016 ◽  
Vol 44 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Jun Ma ◽  
Hong Ren ◽  
Li Lin ◽  
Chunli Zhang ◽  
Zhaohui Wang ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Mainland China ◽  
Clinical Manifestations ◽  
Gitelman Syndrome ◽  
Chinese Patients ◽  
Slc12a3 Gene ◽  
Urine Protein Excretion ◽  
Pathogenic Mutations ◽  
Genetic Features ◽  
Gender Based

Background: Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy caused by inactivating mutations in the SLC12A3 gene. Although hundreds of different mutations across the SLC12A3 gene have been reported worldwide, data from mainland China are limited. We investigated the clinical manifestations and genetic features of Chinese patients with GS. Methods: Fifty-four unrelated Chinese patients with clinically diagnosed GS were included. Clinical manifestations and biochemical parameters were collected and analyzed. All exons and flanking regions of the SLC12A3 and CLCNKB genes were screened by direct sequencing. Results: Weakness was the most commonly reported symptom in this cohort of patients with GS. In gender-based analyses, higher systolic blood pressure and urine protein excretion were observed in male patients. For genetic screening, 2 pathogenic SLC12A3 mutations were identified in 38 patients (70.4%), 1 mutation in 11 patients (20.4%) and no mutation in 5 patients (9.3%). In total, 42 distinct pathogenic mutations throughout SLC12A3 were identified; 16 were novel, including 9 missense, 1 deletion, 1 insertion, 3 splice site and 2 nonsense mutations. Eleven mutations were recurrently found in different patients. Among them, T60M and D486N were identified in 11 individuals. No CLCNKB mutations were found. Conclusion: Sixteen novel SLC12A3 pathogenic mutations were identified in a cohort of Chinese patients with GS. T60M and D486N were most frequent and appear to be important candidate alleles in Chinese patients with GS.

scholarly journals Clinical and Genetic Analyses of 38 Chinese Patients with Peutz-Jeghers Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Bo-Da Wu ◽  
Yong-Jun Wang ◽  
Liang-Liang Fan ◽  
Hui Huang ◽  
Peng Zhou ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Missense Mutations ◽  
Inherited Disease ◽  
Hamartomatous Polyps ◽  
Kaplan Meier ◽  
Genetic Features ◽  
The Difference ◽  
Peutz Jeghers Syndrome

Background. Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by a germline mutation in the STK11 gene. It is characterized by mucocutaneous pigmentation, gastrointestinal hamartomatous polyps, and cancer predisposition. Aims. We aimed to summarize the main clinical and genetic features of Chinese PJS patients and assessed the genotype-phenotype correlations. Methods. Thirty-eight patients clinically diagnosed with Peutz-Jeghers syndrome were included in this study from 2016 to 2019. Combined direct sequencing and multiplex ligation-dependent probe amplification tests were used to detect germline heterogeneous STK11 mutations. RNA sequencing was performed in polyps of PJS patients and control groups to evaluate the difference in expression of STK11. The genotype-phenotype correlations were calculated by Kaplan-Meier analyses. Results. All 26 probands and 12 affected relatives had germline heterogeneous STK11 mutations among which 8 variants were novel. Individuals with missense mutations had their first surgery and other symptoms significantly later than individuals with null mutations. Conclusion. This study expanded the spectrum of STK11 gene mutations and further elucidated individuals with null mutations of STK11 typically had an earlier onset of PJS symptoms and needed earlier management.

scholarly journals Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao-Fang Wang ◽  
Hui Chen ◽  
Peng-Juan Huang ◽  
Zhuo-Kun Feng ◽  
Zi-Qi Hua ◽  
...  
Keyword(s):  
Mutation Detection ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Chinese Patients ◽  
Congenital Nystagmus ◽  
Screening Rate ◽  
Mutation Detection Rate ◽  
Significant Difference ◽  
Phenotype Analysis ◽  
Sporadic Cases

Purpose: Congenital nystagmus (CN) is a genetically and clinically heterogeneous ocular disorder that manifests as involuntary, periodic oscillations of the eyes. To date, only FRMD7 and GPR143 have been reported to be responsible for causing CN. Here, we aimed to identify the disease-causing mutations and describe the clinical features in the affected members in our study.Methods: All the subjects underwent a detailed ophthalmic examination. Direct sequencing of all coding exons and splice site regions in FRMD7 and GPR143 and a mutation assessment were performed in each patient.Results: We found 14 mutations in 14/37 (37.8%) probands, including nine mutations in the FRMD7 gene and five mutations in the GPR143 gene, seven of which are novel, including c.284G&gt;A(R95K), c.964C&gt;T(P322S), c.284+10T&gt;G, c.901T&gt;C (Y301H), and c.2014_2023delTCACCCATGG(S672Pfs*12) in FRMD7, and c.250+1G&gt;C, and c.485G&gt;A (W162*) in GPR143. The mutation detection rate was 87.5% (7/8) of familial vs. 24.1% (7/29) of sporadic cases. Ten mutations in 24 (41.7%) non-syndromic subjects and 4 mutations in 13(30.8%) syndromic subjects were detected. A total of 77.8% (7/9) of mutations in FRMD7 were concentrated within the FERM and FA domains, while all mutations in GPR143 were located in exons 1, 2, 4 and 6. We observed that visual acuity tended to be worse in the GPR143 group than in the FRMD7 group, and no obvious difference in other clinical manifestations was found through comparisons in different groups of patients.Conclusions: This study identified 14 mutations (seven novel and seven known) in eight familial and 29 sporadic patients with congenital nystagmus, expanding the mutational spectrum and validating FRMD7 and GPR143 as mutation hotspots. These findings also revealed a significant difference in the screening rate between different groups of participants, providing new insights for the strategy of genetic screening and early clinical diagnosis of CN.

scholarly journals Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang Jin Kim ◽  
◽  
Kemal Sonmez ◽  
Ryan Swan ◽  
J. Peter Campbell ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Preterm Infants ◽  
Premature Infants ◽  
Retinopathy Of Prematurity ◽  
Smooth Endoplasmic Reticulum ◽  
Enrichment Analysis ◽  
Retinal Disease ◽  
Gene Set Enrichment Analysis ◽  
Whole Exome

AbstractRetinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.

scholarly journals Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeong-Seon Lee ◽  
Joong-Gon Kim ◽  
Soyoung Lee
Keyword(s):  
Polyarteritis Nodosa ◽  
Clinical Manifestations ◽  
Long Term Outcomes ◽  
Childhood Onset ◽  
Laboratory Findings ◽  
Clinical Presentations ◽  
Long Term Prognosis ◽  
Digital Amputation

AbstractChildhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3–17.5), 7.7 (3.5–17.6), and 7.0 (1.6–16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2–32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.

scholarly journals Autoimmune encephalitis in a South Asian population

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nilanka Wickramasinghe ◽  
Dhanushka Dasanayake ◽  
Neelika Malavige ◽  
Rajiva de Silva ◽  
Thashi Chang
Keyword(s):  
Sri Lanka ◽  
Psychiatric Symptoms ◽  
South Asians ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Autoimmune Encephalitis ◽  
Asian Population ◽  
South Asian Population ◽  
Clinical Presentations

Abstract Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

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