Novel and Recurring NOTCH3 Mutations in Two Chinese Patients with CADASIL

2019 ◽  
Vol 19 (1) ◽  
pp. 35-42
Author(s):  
Xiangyu Chen ◽  
Sheng Deng ◽  
Hongbo Xu ◽  
Deren Hou ◽  
Pengzhi Hu ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Han Chinese ◽  
Notch Receptor ◽  
Chinese Patients ◽  
Common Disease ◽  
Common Mutation ◽  
Notch3 Gene ◽  
Genetic Causes

Background: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominant, inherited, systemic, vascular disorder primarily involving the small arteries. It is characterized by migraine, recurrent ischemic strokes, cognitive decline, and dementia. Mutations in the Notch receptor 3 gene (NOTCH3) and the HtrA serine peptidase 1 gene (HTRA1) are 2 genetic causes for CADASIL. The NOTCH3 gene, located on chromosome 19p13.12, is the most common disease-causing gene in CADASIL. Objective: To investigate genetic causes in 2 unrelated Han-Chinese patients with presentations strongly suggestive of CADASIL. Methods: Exome sequencing was performed on both patients and potential pathogenic mutations were validated by Sanger sequencing. Results: This study reports on 2 unrelated Han-Chinese patients with presentations strongly suggestive of CADASIL, identifying that NOTCH3 mutations were the genetic cause. A common mutation, c.268C>T (p.Arg90Cys), and a novel mutation, c.331G>T (p.Gly111Cys) in the NOTCH3 gene, were detected and confirmed in the patients, respectively, and were predicted to be deleterious based on bioinformation analyses. Conclusions: We identified 2 NOTCH3 mutations as likely genetic causes for CADASIL in these 2 patients. Our findings broaden the mutational spectrum of the NOTCH3 gene accountable for CADASIL. Clinical manifestations supplemented with molecular genetic analyses are critical for accurate diagnosis, the provision of genetic counseling, and the development of therapies for CADASIL.

A novel mutation (C271F) in the Notch3 gene in a Chinese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

2007 ◽  
Vol 376 (1-2) ◽  
pp. 229-232 ◽  
Author(s):  
Kam-Ming Au ◽  
Ho-Lun Li ◽  
Bun Sheng ◽  
Tat-Chong Chow ◽  
Mo-Lung Chen ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Notch3 Gene

scholarly journals Novel mutations of PKD1 gene in Chinese patients with autosomal dominant polycystic kidney disease

2002 ◽  
Vol 17 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Lan Ding ◽  
Sizhong Zhang ◽  
Weimin Qiu ◽  
Cuiying Xiao ◽  
Shaoqing Wu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Frameshift Mutation ◽  
Chinese Patients ◽  
Common Disease ◽  
Polycystic Kidney ◽  
Pkd1 Gene ◽  
Autosomal Dominant Polycystic Kidney

Abstract Background. Autosomal dominant polycystic kidney disease (ADPKD) is a common disease in China. The major gene responsible for ADPKD, PKD1, has been fully characterized and shown to encode an integral membrane protein, polycystin 1, which is thought to be involved in cell–cell and cell–matrix interaction. Until now, 82 mutations of PKD1 gene have been reported in European, American, and Asian populations. However, there has been no report on mutations of the PKD1 gene in a Chinese population. Methods. Eighty Chinese patients in 60 families with ADPKD were screened for mutations in the 3′ region of the PKD1 gene using polymerase chain reaction–single-strand conformation polymorphism (PCR–SSCP) and DNA-sequencing techniques. Results. Three mutations were found. The first mutation is a 12593delA frameshift mutation in exon 45, and the polycystin change is 4129WfsX4197, 107 amino acids shorter than the normal polycystin (4302aa). The second mutation is a 12470InsA frameshift mutation in exon 45, producing 4088DfsX4156, and the predicted protein is 148 amino acids shorter than the normal. The third one is a 11151C→T transition in exon 37 converting Pro3648 to Leu. In addition, nine DNA variants, including IVS44delG, were identified. Conclusions. Three mutations in Chinese ADPKD patients are described and all of them are de novo mutations. Data obtained from mutation analysis also suggests that the mutation rate of the 3′ single-copy region of PKD1 in Chinese ADPKD patients is very low, and there are no mutation hot spots in the PKD1 gene. Mutations found in Chinese ADPKD patients, including nucleotide substitution and minor frameshift, are similar to the findings reported by other researchers. Many mutations of the PKD1 gene probably exist in the duplicated region, promoter region, and the introns of PKD1.

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 Novel mutation of the NOTCH3 gene in Arabic family with CADASIL

2011 ◽  
Vol 3 (2) ◽  
pp. 6 ◽  
Author(s):  
Saeed Bohlega
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Vascular Dementia ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Adult Onset ◽  
Notch3 Gene ◽  
Epidermal Growth ◽  
Exon 11

Mutations in the NOTCH3 gene are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an adult onset hereditary angiopathy leading to ischemic stroke, vascular dementia and psychiatric disorders. All mutation of NOTCH3 described so far are striking stereotyped leading to the gain or loss of cystiene residue in a given epidermal growth factor (EGF), like repeat. We report an Arabic family affected with CADASIL mutation, G1790 C, in Exon 11 of the NOTCH3 gene. This is the first novel mutation reported in Arabic CADASIL patients. This finding confirms that mutations in NOTCH3 are associated with the pathogenesis of CADASIL across different ethnic background.

scholarly journals A Novel Mutation in the Notch3 Gene in an Italian Family With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

2001 ◽  
Vol 58 (9) ◽  
pp. 1418 ◽  
Author(s):  
Rosario L. Oliveri ◽  
Maria Muglia ◽  
Nicole De Stefano ◽  
Rosalucia Mazzei ◽  
Angelo Labate ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Notch3 Gene ◽  
Italian Family

TMEM230 Mutations Are Rare in Han Chinese Patients with Autosomal Dominant Parkinson’s Disease

2017 ◽  
Vol 55 (4) ◽  
pp. 2851-2855 ◽  
Author(s):  
Qianqian Wei ◽  
Ruwei Ou ◽  
Qingqing Zhou ◽  
Yongping Chen ◽  
Bei Cao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Dominant ◽  
Han Chinese ◽  
Chinese Patients

scholarly journals Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abram Bunya Kamiza ◽  
Wen-Chang Wang ◽  
Jeng-Fu You ◽  
Reiping Tang ◽  
Huei-Tzu Chien ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cumulative Risk ◽  
Germline Mutations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Mutation Carriers ◽  
Amsterdam Criteria ◽  
Cumulative Risks ◽  
Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

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.

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