Presenilin 1 and APP Gene Mutations in Early-Onset AD Families from a Southeast Region of China

2020 ◽  
Vol 17 (6) ◽  
pp. 540-546
Author(s):  
Jiajia Zhou ◽  
Yi Chen ◽  
Fanxia Meng ◽  
Kan Zhang ◽  
Xiaoyan Liu ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Chinese Population ◽  
Gene Mutations ◽  
Splice Mutation ◽  
Chinese Patients ◽  
Presenilin 1 ◽  
Whole Exome ◽  
Presenilin 2 ◽  
App Gene

Background: Early-Onset Familial Alzheimer’s Disease (EOFAD) has been reported to be associated with Presenilin 1 (PSEN1), Presenilin 2 (PSEN2), and Amyloid Precursor Protein (APP) genes. The spectrum of mutations in Chinese patients with EOFAD was rarely investigated. Objective: To investigate the spectrum of mutations in patients with EOFAD in Chinese population. Methods: We performed whole-exome sequencing and described relevant clinical features in a total of 67 subjects from 3 families with EOFAD. Results: A splice mutation (p.S290C) in PSEN1 and a missense mutation (p.V717I) in APP were identified. Conclusion: The variant p. S290C (c.869-2>G) in PSEN1 in Chinese EOAD family revealed different clinical phenotypes when compared with that of Europeans.

Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland

2003 ◽  
Vol 184 (2) ◽  
pp. 991-996 ◽  
Author(s):  
Cezary Żekanowski ◽  
Maria Styczyńska ◽  
Beata Pepłońska ◽  
Tomasz Gabryelewicz ◽  
Dorota Religa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Precursor Protein ◽  
Presenilin 1 ◽  
Early Onset Alzheimer’S Disease ◽  
Presenilin 2

Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer

2021 ◽  
Author(s):  
Lingyun Zhang ◽  
Zhixiang Ren ◽  
Zhengzheng Su ◽  
Yang Liu ◽  
Tian Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Copy Number ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Anaplastic Thyroid Cancer ◽  
Chinese Patients ◽  
Driver Gene ◽  
Phosphatidylinositol 3 Kinase ◽  
Entire Cohort ◽  
Whole Exome

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

scholarly journals Delineation of molecular findings by whole exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

2020 ◽  
Author(s):  
Mandy Ho-Yin Tsang ◽  
Anna Ka-Yee Kwong ◽  
Kate Lok-San Chan ◽  
Jasmine Lee-Fong Fung ◽  
Mullin Ho-Chung Yu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Population ◽  
Founder Mutation ◽  
Diagnostic Yield ◽  
Genetic Diagnosis ◽  
Mitochondrial Diseases ◽  
Chinese Patients ◽  
Southern Chinese ◽  
Whole Exome

Abstract BackgroundMitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs.MethodsWe recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines.ResultsSixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n=3, two were siblings), ALDH5A1 , ARX , FA2H , KCNT1 , LDHD , NEFL , NKX2-2 , TBCK , and WAC.ConclusionsWe confirmed that the COQ4 :c.370G>A, p.(Gly124Ser) variant was a recurrent founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

scholarly journals Delineation of molecular findings by whole exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

2020 ◽  
Author(s):  
Mandy Ho-Yin Tsang ◽  
Anna Ka-Yee Kwong ◽  
Kate Lok-San Chan ◽  
Jasmine Lee-Fong Fung ◽  
Mullin Ho-Chung Yu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Population ◽  
Founder Mutation ◽  
Diagnostic Yield ◽  
Genetic Diagnosis ◽  
Mitochondrial Diseases ◽  
Chinese Patients ◽  
Southern Chinese ◽  
Whole Exome

Abstract Background Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs.Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines.Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n=3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC.Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant was a recurrent founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

Probable Novel PSEN1 Gln222Leu Mutation in a Chinese Family with Early-Onset Alzheimer's Disease

2019 ◽  
Vol 16 (8) ◽  
pp. 764-769 ◽  
Author(s):  
Huayuan Wang ◽  
Ruihua Sun ◽  
Yingying Shi ◽  
Mingrong Xia ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Missense Mutation ◽  
Early Onset ◽  
Sanger Sequencing ◽  
Pathogenic Mutation ◽  
Presenilin 1 ◽  
Chinese Family ◽  
Whole Exome ◽  
Early Onset Alzheimer’S Disease

Background: The rate of occurrence of Alzheimer’s disease is increasing around the world. However, there is still no significant breakthrough in the study of its etiology and pathogenesis. Objective: To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer software. Method: Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing were performed in the proband. Mutation sites were verified in 158 subjects. Results: We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected family members, 50 sporadic Alzheimer's disease patients and 100 control subjects. Conclusion: A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer’s disease has been reported, besides， it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer’s disease.

scholarly journals Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Mandy H.Y. Tsang ◽  
Anna K.Y. Kwong ◽  
Kate L.S. Chan ◽  
Jasmine L.F. Fung ◽  
Mullin H.C. Yu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Population ◽  
Founder Mutation ◽  
Diagnostic Yield ◽  
Genetic Diagnosis ◽  
Mitochondrial Diseases ◽  
Chinese Patients ◽  
Southern Chinese ◽  
Whole Exome

Abstract Background Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

scholarly journals Comprehensive Analysis of LIN28A in Chinese Patients With Early Onset Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojing Gu ◽  
Yanbing Hou ◽  
Yongping Chen ◽  
Ruwei Ou ◽  
Bei Cao ◽  
...  
Keyword(s):  
Early Onset ◽  
Chinese Patient ◽  
Chinese Patients ◽  
Loss Of Function ◽  
Developmental Defects ◽  
Functional Studies ◽  
Whole Exome ◽  
Increased Risk ◽  
Related Phenotype ◽  
Early Onset Parkinson’S Disease

A loss-of-function variant in Lin-28 Homolog A gene (LIN28A p. R192G, rs558060339) has been identified in two East Asian ancestry patients with early-onset PD (EOPD). Functional studies revealed that such a variant could lead to developmental defects and PD-related phenotype, and the phenotypes could be rescued after correction of the variant. The aim of the study was to screen the variants of LIN28A in Chinese patients with EOPD. A total of 682 EOPD patients were sequenced with whole exome sequencing and the coding and flanking region of LIN28A were analyzed. We identified a rare coding variant, p. P182L, of LIN28A in a Chinese patient with EOPD. Moreover, we also found a 3′-UTR polymorphism (rs4659441) to be associated with an increased risk for PD. However, our rare variant burden analysis did not support a role for LIN28A as a major causal gene for PD.

scholarly journals Genotyping of Five Chinese Patients with 17α-Hydroxylase Deficiency Diagnosed through High-Performance Liquid Chromatography Serum Adrenal Profile: Identification of Two Novel CYP17 Mutations

2006 ◽  
Vol 91 (9) ◽  
pp. 3647-3653 ◽  
Author(s):  
Ji-Qing Wei ◽  
Ji-Lu Wei ◽  
Wei-Chun Li ◽  
Yun-Sheng Bi ◽  
Feng-Cai Wei
Keyword(s):  
Chinese Population ◽  
High Performance ◽  
Gene Mutations ◽  
Diagnostic Value ◽  
Chinese Patients ◽  
Chinese Family ◽  
Hydroxylase Deficiency ◽  
Chinese Families ◽  
Cyp17 Gene ◽  
Qilu Hospital

Abstract Context: 17α-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia caused by CYP17 gene mutations. Objective: Five Chinese patients with 17α-hydroxylase deficiency were genotyped. Patients: The five patients derived from four families living in Shandong Province, China. The diagnosis of 17α-hydroxylase deficiency was initially established through HPLC serum adrenal profiles in Qilu Hospital, China, from 1983–1993. Results: Three CYP17 gene mutations were identified from these patients. Among them, V311fs and Y329fs are two novel frame-shifting mutations. V311fs is an 8-bp nucleotide (TTAAATGG) deletion in exon 5. Y329fs is a deletion-insertion combined mutation (TAC→AA) at codon 329 in exon 6. Two homozygotes for Y329fs and one compound heterozygote for Y329fs and V311fs were identified from three different families. Two homozygous sisters for the D487_S488_F489 deletion were identified. Conclusion: The results confirmed the diagnostic value of the HPLC serum adrenal profile for 17α-hydroxylase deficiency. The D487_S488_F489 deletion had been identified in two previously genotyped Chinese families. In our present study, a third Chinese family with this mutation was identified, suggesting that this mutation is a prevalent CYP17 mutation in the Chinese population. The identification of Y329fs mutation in addition to three previously identified mutations at codon 329 suggests that codon 329 is an unstable point of the CYP17 gene. The mutations identified from our five patients appear to be random, but the recurrence of the Y329fs mutation may be attributed to a founder effect. Our studies suggest that 17α-hydroxylase deficiency may not be rare in the Chinese population.

Sign in / Sign up

Export Citation Format

Share Document