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 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 Genetic Analysis of SLC12A3 Gene in Chinese Patients with Gitelman Syndrome

2019 ◽  
Vol 25 ◽  
pp. 5942-5952 ◽  
Author(s):  
Yanmei Zeng ◽  
Ping Li ◽  
Shu Fang ◽  
Chunyan Wu ◽  
Yudan Zhang ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Gitelman Syndrome ◽  
Chinese Patients ◽  
Slc12a3 Gene

scholarly journals Non-O1/non-O139 Vibrio cholerae bacteraemia in mainland China from 2005 to 2019: clinical, epidemiological and genetic characteristics

2020 ◽  
Vol 148 ◽  
Author(s):  
Xinyao Li ◽  
Yuanyuan Wu ◽  
Xiaojun Sun ◽  
Jianping Ma ◽  
Xiaofeng Li ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Antimicrobial Agents ◽  
Clinical Epidemiology ◽  
Yangtze River Basin ◽  
Mainland China ◽  
Clinical Manifestations ◽  
Molecular Characteristics ◽  
Malignant Tumours ◽  
Genetic Characteristics ◽  
Genetic Features

Abstract In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139 Vibrio cholerae (NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June–August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate that ctxAB and tcpA genes were absent in all NOVC isolates but other putative virulence genes (hlyA, toxR, hap and rtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

scholarly journals Clinical and genetic characteristics of Chinese patients with cerebrotendinous xanthomatosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qing-Qing Tao ◽  
Yun Zhang ◽  
Hui-Xia Lin ◽  
Hai-Lin Dong ◽  
Wang Ni ◽  
...  
Keyword(s):  
Chinese Population ◽  
Autosomal Recessive ◽  
Storage Disease ◽  
Clinical Manifestations ◽  
Cerebrotendinous Xanthomatosis ◽  
Chinese Patients ◽  
Lipid Storage Disease ◽  
Genetic Characteristics ◽  
Pathogenic Mutations ◽  
Autosomal Recessive Pattern

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare inborn lipid-storage disease caused by mutations in the sterol 27-hydroxylase (CYP27A1) gene with an autosomal recessive pattern of inheritance. To date, only 19 CTX patients from 16 families have been reported in the Chinese population. Results Three novel likely pathogenic mutations (c.368_374delCCAGTAC, c.389 T > A and c.571C > T) and 7 previously reported pathogenic mutations (c.379C > T, c.435G > T, c.1016C > T, c.1214G > A, c.1263 + 1G > A, c.1420C > T and c.1435C > T) were identified. In addition, we summarized the genotypes and phenotypes of reported Chinese CTX patients. The most predominant mutations in CYP27A1 were c.410G > A and c.379C > T, and the most common clinical manifestations were pyramidal signs, xanthomatosis, cerebellar ataxia, and cognitive impairment. Conclusion Our study broadens the genetic and clinical spectrum of CTX and provides insightful information to help better diagnose and understand the disease.

Clinico-genetic specifications of Bartter and Gitelman syndrome in children

2020 ◽  
Vol 24 (3) ◽  
pp. 42-53
Author(s):  
J. G. Leviashvili ◽  
N. D. Savenkova
Keyword(s):  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Bartter Syndrome ◽  
Gitelman Syndrome ◽  
School Age ◽  
Electrolyte Disturbances ◽  
New Genes ◽  
Hypokalemic Alkalosis ◽  
Genetic Features ◽  
Adolescents And Adults

Molecular genetic research has led to the discovery of new genes encoding proteins – transporters, cotransporters and exchangers involved in the transport of sodium, potassium and chlorine in the thick ascending part of the Henle loop and in the distal convoluted tubule. The article presents modern literature data on the genetic types of tubulopathy with the leading syndrome of hypokalemia and alkalosis – Bartter and Gitelman syndromes in children. The clinical and genetic features of the six types of Bartter syndrome with autosomal recessive and X-linked inheritance, classification approaches, diagnosis, and modern treatment methods are described. Since the first description of Bartter syndrome, 6 clinical genetic options have been known, including antenatal I, II, IVa, IVb, V types, which are potentially life-threatening diseases. Bartter type III syndrome is characterized by the manifestation of hypokalemic alkalosis in children at an early and preschool age. Treatment of Bartter syndrome in children includes the correction of water – electrolyte disturbances, the use of non-steroidal anti-inflammatory drugs (NSAIDs) to inhibit the excessive formation of renal prostaglandin PgE 2. Gitelman syndrome with an autosomal recessive type of inheritance manifests itself in children at school age, later on in adolescents and adults there is an increase in clinical manifestations (with severe hypomagnesemic seizures of the upper and lower extremities, arterial hypertension) requiring correction. The review presents the clinical and genetic features of the rare, atypical form of the autosomal recessive Gitelman syndrome with a manifestation in school age, which is characterized by progressive bilateral calcifications of the subcortical parts of the cerebral hemispheres, calcifications in the basal ganglia and subcortical cerebellum. Unlike Bartter syndrome, with more severe clinical manifestations in newborns, infants and young children, Gitelman syndrome tends to increase clinical manifestations in adolescents and adults. Treatment of Gitelman syndrome in children and adolescents includes the correction of water – electrolyte disturbances, the use of magnesium preparations and salt subsidy.

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>A(R95K), c.964C>T(P322S), c.284+10T>G, c.901T>C (Y301H), and c.2014_2023delTCACCCATGG(S672Pfs*12) in FRMD7, and c.250+1G>C, and c.485G>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 Birt–Hogg–Dubé syndrome in Chinese patients: a literature review of 120 families

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaowen Hu ◽  
Guofeng Zhang ◽  
Xianmeng Chen ◽  
Kai-Feng Xu
Keyword(s):  
Spontaneous Pneumothorax ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Lower Lobe ◽  
Skin Lesions ◽  
Jiangsu Province ◽  
Chinese Patients ◽  
Renal Tumors ◽  
Pulmonary Cysts ◽  
Exon 11

Abstract Objective To clarify the epidemiological and clinical features of Birt–Hogg–Dubé syndrome (BHDS) in Chinese patients. Methods We identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2008 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded. Results Twenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0 ± 13.9 years (range, 18–84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1–6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%). Conclusions Although BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

Mucopolysaccharidosis III in Mainland China: natural history, clinical and molecular characteristics of 34 patients

2020 ◽  
Vol 33 (6) ◽  
pp. 793-802 ◽  
Author(s):  
Weijing Kong ◽  
Yan Meng ◽  
Liping Zou ◽  
Guang Yang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Autosomal Recessive ◽  
Mainland China ◽  
Clinical Manifestations ◽  
Hereditary Disease ◽  
Molecular Characteristics ◽  
Speech Delay ◽  
Initial Symptoms ◽  
Mps Iii ◽  
Mps Iiia

AbstractObjectivesSanfilippo syndrome (Mucopolysaccharidosis III, MPS III) is a rare autosomal recessive hereditary disease, which is caused by lysosomal enzyme deficiency. This study was operated to investigate clinical and molecular characteristics of patients with MPS III, which will improve the diagnosis and treatment of MPS III.MethodThirty four patients with MPS III were assessed using clinical evaluation, questionnaire, and scoring system.ResultsAmong the 34 patients, 14 had MPS IIIA, 19 had MPS III B, and one had MPS III C. Speech delay (100%) and intellectual disability (100%) were the most prevalent clinical manifestations in this cohort, followed by hyperactivity (94.12%), hirsutism (91.18%), enlarged head circumference (73.52%), repeated diarrhea (67.64%), sparse teeth (67.64%), and Mongolian spots (64.71%). There were two clinical manifestations that were significantly different between IIIA and IIIB: Hepatosplenomegaly and serrated teeth. The most common initial symptoms at diagnosis were speech delay (52.94%), hyperactivity (35.29%), and mental retardation (29.41%). Genetic analysis of 25 patients was conducted, which identified 12 novel mutations.ConclusionWhen language retardation, mental retardation, and rough facial features occurred, MPS III should be considered. At same time, more examination should be operated, such as examination of changes in cranial magnetic resonance imaging of cerebral cortex atrophy. Hepatosplenomegaly and serrated teeth could be used clinically to preliminarily distinguish IIIA from IIIB.

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