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

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.

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.

Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy

2019 ◽  
Vol 104 (6) ◽  
pp. 846-851 ◽  
Author(s):  
Feng-Juan Gao ◽  
Yu-He Qi ◽  
Fang-Yuan Hu ◽  
Dan-Dan Wang ◽  
Ping Xu ◽  
...  
Keyword(s):  
De Novo ◽  
Population Based ◽  
Mutation Spectrum ◽  
Chinese Patients ◽  
Macular Dystrophy ◽  
De Novo Mutations ◽  
Panel Testing ◽  
Chinese Origin ◽  
Wide Range ◽  
Distinct Disease

BackgroundBestrophin-1 (BEST1) gene is associated with a wide range of ocular phenotypes, collectively termed as bestrophinopathy. The aim of the current study was to identify the mutation spectrum of BEST1 in a large cohort of Chinese patients with bestrophinopathy.MethodsPatients clinically suspected of bestrophinopathy were screened using multigene panel testing. All BEST1 variants were confirmed by Sanger sequencing, and validated in the families.FindingsA total of 92 patients (Best vitelliform macular dystrophy (BVMD)=77; autosomal recessive bestrophinopathy (ARB)=15) from 58 unrelated families of Chinese origin and their available family members (n=65) were recruited. Overall, 39 distinct disease-causing BEST1 variants were identified, including 13 novel variants, and two reported variants but novel for ARB. Of them, 14 were associated with ARB, 23 with BVMD and two (c.604C>T and c.898G>A) with both BVMD and ARB. Most mutations associated with BVMD were missense (97.78%), while ARB was associated with more complex mutations, including missense (88.46%), splicing effect (3.85%), and frameshifts (15.38%). BEST1 hotspots were c.898G>A and c.584C>T among BVMD and ARB patients, respectively. Hot regions were located in exons 8, 2 and 6 in BVMD patients, and in exons 5 and 7 in ARB patients. The overall penetrance of BEST1 in our cohort was 71.30%, no de novo mutations were identified.ConclusionThis is the largest study to date that provides major population-based data of the BEST1 mutation spectrum in China. Our results can serve as a well-founded reference for genetic counselling for patients with bestrophinopathy of Chinese origin.

Sign in / Sign up

Export Citation Format

Share Document