Hydroa vacciniforme-like lymphoproliferative disorder: A study of clinicopathology and whole-exome sequencing in Chinese patients

Abstract Degenerative lumbar spinal stenosis (DLSS) is a common lumbar disease requiring surgery. Previous studies indicate that genetic mutation may play a part in DLSS. However, there is scarcely specific study regarding the genetic study for DLSS. Whole exome sequencing (WES) is an effective strategy to search for disease-causing genes. To identify probable susceptible genes, we performed a WES in a cohort of 50 patients and 25 controls with DLSS. By bioinformatics analyses, we successfully identified several novel variants including HLA-DRB1, PARK2, ACTR8, AOAH, BCORL1, MKRN2, NRG4, NUP205, etc. To the best of our knowledge, this is the first genetic study of susceptibility genes with DLSS by WES in Chinese patients. In conclusion, our findings revealed that deleterious mutations in these genes may contribute to the development of DLSS.

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

10.21203/rs.3.rs-23585/v2 ◽

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.

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

10.21203/rs.3.rs-23585/v1 ◽

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.

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

Human Genomics ◽

10.1186/s40246-020-00278-0 ◽

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.

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Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia

10.21203/rs.3.rs-156279/v2 ◽

2021 ◽

Author(s):

Yutian Ye ◽

Qijun Huang ◽

Lipeng Chen ◽

Chunxian Liang ◽

Kaixue Zhuang ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Primary Ciliary Dyskinesia ◽

Rare Variants ◽

Genetic Disorders ◽

Autosomal Recessive Disorder ◽

Bioinformatic Analysis ◽

Chinese Patients ◽

Whole Exome ◽

Ciliary Dyskinesia

Abstract Background Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder. The genetic factors contributing to PCD pathogenesis remain elusive for approximately 20–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of sporadic PCD genes using whole-exome sequencing (WES). Result All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy (TEM) images of cilia. WES and bioinformatic analysis were then conducted for patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 15 rare variants were identified in five patients with PCD. Five new variants of CCDC40, DNAH1, DNAAF3, and DNAI1 were considered causative variants and included one splicing and three homozygous variants. Conclusion Our study demonstrated that patients with PCD carry rare causative variants of multiple genes. Our findings indicated that not only known causative genes but also other functional genes should be considered for heterogeneous genetic disorders.

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Identification of Novel Gene Mutations in Degenerative Lumbar Spinal Stenosis Using Whole Exome Sequencing in Chinese Population

10.21203/rs.3.rs-41775/v1 ◽

2020 ◽

Author(s):

Xin Jiang ◽

Dong Chen

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Spinal Stenosis ◽

Lumbar Spinal Stenosis ◽

Genetic Study ◽

Chinese Patients ◽

Bioinformatics Analyses ◽

Degenerative Lumbar Spinal Stenosis ◽

Whole Exome ◽

Lumbar Spinal

Abstract Degenerative lumbar spinal stenosis (DLSS) is a common lumbar disease requiring surgery. Previous studies indicate that genetic mutation may play a part in DLSS. However, there is scarcely specific study regarding the genetic study for DLSS. Whole exome sequencing (WES) is an effective strategy to search for disease-causing genes. To identify probable susceptible genes, we performed a WES in a cohort of 50 patients and 25 controls with DLSS. By bioinformatics analyses, we successfully identified several novel variants including HLA-DRB1, PARK2, ACTR8, AOAH, BCORL1, MKRN2, NRG4, NUP205, etc. To the best of our knowledge, this is the first genetic study of susceptibility genes with DLSS by WES in Chinese patients. In conclusion, our findings revealed that deleterious mutations in these genes may contribute to the development of DLSS.

Download Full-text