scholarly journals De novo 22q11.2 deletions and auricular findings in two Chinese patients with microtia

2021 ◽  
Author(s):  
Nuo Si ◽  
Zeya Zhang ◽  
Xin Huang ◽  
Chanchen Wang ◽  
Peipei Guo ◽  
...  
Keyword(s):  
De Novo ◽  
Chinese Patients

scholarly journals Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders

2021 ◽  
Author(s):  
Yi Zhang ◽  
Tao Wang ◽  
Yan Wang ◽  
Kun Xia ◽  
Jinchen Li ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Neurodevelopmental Disorders ◽  
De Novo ◽  
Genetic Data ◽  
Chinese Patients ◽  
The Novel ◽  
Mutational Spectrum ◽  
Functional Variants ◽  
Public Data ◽  
Chromosomal Genes

AbstractNeurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.

Identification of two de novo mutations in Chinese patients with X-linked adrenoleukodystrophy

2008 ◽  
Vol 46 (12) ◽  
Author(s):  
Zhihong Wang ◽  
Longfeng Ke ◽  
Aizhen Yan ◽  
Zhongyong Zhu ◽  
Fenghua Lan
Keyword(s):  
De Novo ◽  
Chinese Patients ◽  
De Novo Mutations

Prognostic value of the multidrug resistance transporter ABCG2 gene polymorphisms in Chinese patients with de novo acute leukaemia

2011 ◽  
Vol 47 (13) ◽  
pp. 1990-1999 ◽  
Author(s):  
Fang Wang ◽  
Yong-ju Liang ◽  
Xing-ping Wu ◽  
Li-ming Chen ◽  
Kenneth Kin Wah To ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Acute Leukaemia ◽  
Gene Polymorphisms ◽  
Prognostic Value ◽  
De Novo ◽  
Chinese Patients ◽  
Multidrug Resistance Transporter ◽  
Abcg2 Gene

scholarly journals Genetic Spectrum and Clinical Features in a Cohort of Chinese Patients with Autosomal Recessive Cerebellar Ataxias

2021 ◽  
Author(s):  
Hao-Ling Cheng ◽  
Ya-Ru Shao ◽  
Yi Dong ◽  
Hai-Lin Dong ◽  
Lu Yang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Autosomal Recessive ◽  
High Efficiency ◽  
De Novo ◽  
Uniparental Disomy ◽  
Genetic Diagnosis ◽  
Chinese Patients ◽  
Molecular Diagnostic ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
Clinical Profiles

Abstract Background: Although many causative genes have been uncovered in recent years, genetic diagnosis is still missing for approximately 50% of autosomal recessive cerebellar ataxia (ARCA) patients. Few studies have been performed to determine the genetic spectrum and clinical profiles of ARCA patients in the Chinese population.Methods: Fifty-four Chinese index patients with unexplained autosomal recessive or sporadic ataxia were investigated by whole-exome sequencing (WES) and copy number variation (CNV) calling with Exome Depth. Likely causal CNV predictions were validated by CNVseq. Results: Thirty-eight mutations including 29 novel ones were identified in 25 out of 54 patients, providing a 46.3% positive molecular diagnostic rate. Ten different genes were involved, and the four most common genes were SACS, SYNE1, ADCK3 and SETX, which accounted for 76.0% (19/25) of the positive cases. The de novo microdeletion in SACS was firstly reported in China and the uniparental disomy of ADCK3 was reported for the first time worldwide. Furthermore, the clinical features of the patients carrying SACS, SYNE1and ADCK3 mutations were summarized. Conclusions: Our results expand the genetic spectrum and clinical profiles of ARCA patients, demonstrate the high efficiency and reliability of WES combined CNV analysis in diagnosing suspected ARCA, and emphasize the importance of complete bioinformatics analysis of WES data in making an accurate diagnosis.

Retrospective analysis of 36 fusion genes in 2479 Chinese patients of de novo acute lymphoblastic leukemia

2018 ◽  
Vol 72 ◽  
pp. 99-104 ◽  
Author(s):  
Xue Chen ◽  
Fang Wang ◽  
Yang Zhang ◽  
Mangju Wang ◽  
Wenjun Tian ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Retrospective Analysis ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Chinese Patients ◽  
Fusion Genes

scholarly journals Clinical and Molecular Spectrum of Glutamate Dehydrogenase Gene Defects in 26 Chinese Congenital Hyperinsulinemia Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Chang Su ◽  
Xue-Jun Liang ◽  
Wen-Jing Li ◽  
Di Wu ◽  
Min Liu ◽  
...  
Keyword(s):  
Glutamate Dehydrogenase ◽  
De Novo ◽  
Mutational Analysis ◽  
Age At Onset ◽  
Normal Serum ◽  
Protein Restriction ◽  
Chinese Patients ◽  
Congenital Hyperinsulinism ◽  
Missense Mutations ◽  
De Novo Mutations

Objective. To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Methods. The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. Results. Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 μmol/L (range: 37–190 μmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. Conclusions. Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.

scholarly journals Restoration of β-globin expression with optimally designed lentiviral vector for β-thalassemia treatment in Chinese patients

2020 ◽  
Author(s):  
Wenjie Ouyang ◽  
Guoyi Dong ◽  
Weihua Zhao ◽  
Jing Li ◽  
Ziheng Zhou ◽  
...  
Keyword(s):  
Gene Therapy ◽  
De Novo ◽  
Lentiviral Vector ◽  
Therapeutic Option ◽  
Globin Gene ◽  
Chinese Patients ◽  
Common Mutation ◽  
Minimal Risk ◽  
Hematopoietic Stem ◽  
Starting Point

Abstractβ-thalassemia is one of the most prevalent genetic diseases worldwide. The current treatment for β–thalassemia is allogeneic hematopoietic stem cell transplantation (HSCT), which is limited due to lack of matched donors. Gene therapy has been developed as an alternative therapeutic option for transfusion-ependent β-thalassemia (TDT). However, successful gene therapy for β-thalassemia patients in China has not been reported. Here we present the results of preclinical studies of an optimally designed LV named LentiHBBT87Q in hematopoietic stem cells (HSCs) derived from Chinese TDT patients. LentiHBBT87Q was selected from a series of LVs with optimized backbone and de novo cloning strategy. It contains an exogenous T87Q β-globin gene (HBBT87Q) driven by a specific reconstituted locus control region (rLCR) and efficiently express HBB mRNA and HBB protein in erythroblasts derived from cord blood (CB) HSCs. To facilitate clinical transformation, we manufactured clinical grade LentiHBBT87Q (cLentiHBBT87Q) and optimized its transduction procedure. Importantly, transduction of cLentiHBBT87Qrestored expression of HBB monomer and adult hemoglobin (HbA) tetramer to relatively normal level in erythroblasts from bone marrow (BM) HSCs of Chinese TDT patients, that carry the most common mutation types and cover various genotypes, including β0/β0. Furthermore, viral integration sites (VIS) of cLentiHBBT87Q were similar to other LVs safely used in previous clinical trials and the associated risk of tumorigenesis was not observed in cLentiHBBT87Q transduced HSCs through comprehensive analysis. Taken together, we have engineered the cLentiHBBT87Q that can restore β-globin expression in the HSCs-derived erythroblasts of Chinese TDT patients with minimal risk on tumorigenesis, providing a favorable starting point for future clinical application.

scholarly journals Genetic spectrum and clinical features in a cohort of Chinese patients with autosomal recessive cerebellar ataxias

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Hao-Ling Cheng ◽  
Ya-Ru Shao ◽  
Yi Dong ◽  
Hai-Lin Dong ◽  
Lu Yang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Autosomal Recessive ◽  
High Efficiency ◽  
De Novo ◽  
Uniparental Disomy ◽  
Genetic Diagnosis ◽  
Chinese Patients ◽  
Molecular Diagnostic ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
First Time

Abstract Background Although many causative genes have been uncovered in recent years, genetic diagnosis is still missing for approximately 50% of autosomal recessive cerebellar ataxia (ARCA) patients. Few studies have been performed to determine the genetic spectrum and clinical profile of ARCA patients in the Chinese population. Methods Fifty-four Chinese index patients with unexplained autosomal recessive or sporadic ataxia were investigated by whole-exome sequencing (WES) and copy number variation (CNV) calling with ExomeDepth. Likely causal CNV predictions were validated by CNVseq. Results Thirty-eight mutations including 29 novel ones were identified in 25 out of the 54 patients, providing a 46.3% positive molecular diagnostic rate. Ten different genes were involved, of which four most common genes were SACS, SYNE1, ADCK3 and SETX, which accounted for 76.0% (19/25) of the positive cases. The de novo microdeletion in SACS was reported for the first time in China and the uniparental disomy of ADCK3 was reported for the first time worldwide. Clinical features of the patients carrying SACS, SYNE1 and ADCK3 mutations were summarized. Conclusions Our results expand the genetic spectrum and clinical profiles of ARCA patients, demonstrate the high efficiency and reliability of WES combined with CNV analysis in the diagnosis of suspected ARCA, and emphasize the importance of complete bioinformatics analysis of WES data for accurate diagnosis.

Multimodal Imaging and Genetic Characteristics of Chinese Patients with USH2A-Associated Nonsyndromic Retinitis Pigmentosa

2020 ◽  
Author(s):  
Chong Chen ◽  
Qiao Sun ◽  
Mingmin Gu ◽  
Tianwei Qian ◽  
Dawei Luo ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
De Novo ◽  
Molecular Genetic ◽  
In Silico Analysis ◽  
Chinese Patients ◽  
Insertion Mutation ◽  
Missense Mutations ◽  
De Novo Mutations ◽  
Cross Sectional ◽  
Genetic Characteristics

Abstract Background To determine the clinical characteristics and molecular genetic background responsible for USH2A mutations associated with nonsyndromic retinitis pigmentosa (RP) in five Chinese families, a retrospective cross-sectional study was performed. Data of detailed history and comprehensive ophthalmological examinations were extracted from medical charts. Genomic DNA was sequenced by whole-exome sequencing. The pathogenicity predictions were evaluated by in silico analysis. The structural modeling of the wide-type and mutant USH2A proteins was displayed based on I-Tasser software.Results The ultrawide-field fundus imaging showed a distinctive pattern of hyperautofluorescence in the parafoveal ring with macular sparing. Ten USH2A variants were detected, including seven missense mutations, two splicing mutations and one insertion mutation. Six of these variants have already been reported, and the remaining four were novel. Of the de novo mutations, the p.C931Y and p.G4489S mutations were predicted to be deleterious or probably damaging; the p.M4853V mutation was predicted to be neutral or benign; and the IVS22+3A>G mutation was a splicing mutation that could influence mRNA splicing and affect the formation of the hairpin structure of the USH2A protein.Conclusions Our data further confirm that USH2A plays a pivotal role in the maintenance of photoreceptors and expand the spectrum of USH2A mutations that are associated with nonsyndromic RP in Chinese patients.

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