scholarly journals Large scale genotype phenotype correlation analysis based on phylogenetic trees

2007 ◽  
Vol 23 (7) ◽  
pp. 785-788 ◽  
Author(s):  
F. Habib ◽  
A. D. Johnson ◽  
R. Bundschuh ◽  
D. Janies
Keyword(s):  
Correlation Analysis ◽  
Phylogenetic Trees ◽  
Large Scale ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

Spectrum of ATP7B mutations and genotype-phenotype correlation in large-scale Chinese patients with Wilson Disease

2017 ◽  
Vol 92 (1) ◽  
pp. 69-79 ◽  
Author(s):  
N. Cheng ◽  
H. Wang ◽  
W. Wu ◽  
R. Yang ◽  
L. Liu ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Large Scale ◽  
Chinese Patients ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

scholarly journals Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease

2021 ◽  
Author(s):  
Mingming Li ◽  
Jing Ma ◽  
Wenlong Wang ◽  
Xu Yang ◽  
Kaizhong Luo
Keyword(s):  
Wilson Disease ◽  
Large Scale ◽  
Allelic Frequency ◽  
Chinese Patients ◽  
Missense Mutations ◽  
Onset Age ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Nonsense Mutations ◽  
Genotype Phenotype Correlation

Abstract AIM To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype-phenotype correlation in a large-scale sample of Chinese WD patients. Methods One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype-phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.Results In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 7 mutations had not been previously reported: 1510_1511insA, 2075T>C (Leu692Pro), 2233C>A (Leu745Met), 3209C>G (Pro1070Arg),3677C>T (Thr1226Ile), 3793G>T (Val1265Leu) and 3824T>C (Leu1275Ser). The 2333G>T (Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by 2975C>T (Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The 2333G>T (Arg778 Leu) and 2975C>T (Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hot spot exons. Phenotype-genotype correlation analysis suggested that 2333G>T (Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P=0.034). 2975C>T (Pro992Leu) was correlated with earlier age of disease onset (P=0.002). Additionally, we found that the 3809A>G (Asn1270Ser) mutation significantly indicated younger onset age (P=0.012), and the 3884C>T (Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P=0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P=0.039, P=0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations. Conclusion In this study, we identified seven novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.

scholarly journals Genotype-phenotype correlation analysis and therapeutic development using a patient stem cell-derived disease model of Wolfram syndrome

2021 ◽  
Author(s):  
Rie Asada Kitamura ◽  
Kristina Maxwell ◽  
Wenjuan Ye ◽  
Kelly Kries ◽  
Cris Brown ◽  
...  
Keyword(s):  
Stem Cell ◽  
Correlation Analysis ◽  
Combination Treatment ◽  
Disease Model ◽  
Wolfram Syndrome ◽  
Phenotype Correlation ◽  
Chemical Chaperones ◽  
Pathogenic Variants ◽  
Genotype Phenotype Correlation ◽  
Therapeutic Development

Wolfram syndrome is a rare genetic disorder largely caused by pathogenic variants in the WFS1 gene and manifested by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Recent genetic and clinical findings have revealed Wolfram syndrome as a spectrum disorder. Therefore, a genotype-phenotype correlation analysis is needed for diagnosis and therapeutic development. Here, we focus on the WFS1 c.1672C>T, p.R558C variant which is highly prevalent in the Ashkenazi-Jewish population. Clinical investigation indicates that subjects carrying the homozygous WFS1 c.1672C>T, p.R558C variant show mild forms of Wolfram syndrome phenotypes. Expression of WFS1 p.R558C is more stable compared to the other known recessive pathogenic variants associated with Wolfram syndrome. Stem cell-derived islets (SC-islets) homozygous for WFS1 c.1672C>T variant recapitulates genotype-related Wolfram phenotypes, which are milder than those of SC-islets with compound heterozygous WFS1 c.1672C>T (p.R558C), c.2654C>T (p.P885L). Enhancing residual WFS1 function by a combination treatment of chemical chaperones, sodium 4-phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), mitigates detrimental effects caused by the WFS1 c.1672C>T, p.R558C variant and restored SC-islet function. Thus, the WFS1 c.1672C>T, p.R558C variant causes a mild form of Wolfram syndrome phenotypes, which can be remitted with a combination treatment of chemical chaperones. We demonstrate that our patient stem cell-derived disease model provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.

Genotype-phenotype correlation analysis in GNE myopathy

2017 ◽  
Vol 27 ◽  
pp. S41
Author(s):  
O. Pogoryelova ◽  
P. Cammish ◽  
H. Mansbach ◽  
H. Lochmüller
Keyword(s):  
Correlation Analysis ◽  
Phenotype Correlation ◽  
Gne Myopathy ◽  
Genotype Phenotype Correlation

scholarly journals NGS analysis in Marfan syndrome spectrum: Combination of rare and common genetic variants to improve genotype-phenotype correlation analysis

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222506 ◽  
Author(s):  
Davide Gentilini ◽  
Antonino Oliveri ◽  
Teresa Fazia ◽  
Alessandro Pini ◽  
Susan Marelli ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Marfan Syndrome ◽  
Genetic Variants ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Common Genetic Variants

Genotype-phenotype correlation analysis in GNE myopathy

2017 ◽  
Vol 27 ◽  
pp. S149
Author(s):  
O. Pogoryelova ◽  
P. Cammish ◽  
H. Mansbach ◽  
H. Lochmüller
Keyword(s):  
Correlation Analysis ◽  
Phenotype Correlation ◽  
Gne Myopathy ◽  
Genotype Phenotype Correlation
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