scholarly journals Identification of a Novel Mutation in the KITLG Gene in a Chinese Family with Familial Progressive Hyper- and Hypopigmentation

2020 ◽  
Author(s):  
Jianbo Wang ◽  
Weisheng Li ◽  
Naihui Zhou ◽  
Shoumin Zhang ◽  
Xueli Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Skin Disorder ◽  
Novel Mutation ◽  
Protein Structures ◽  
Three Dimensional ◽  
Recurrent Mutation ◽  
Chinese Family ◽  
Exon 2 ◽  
Kit Ligand ◽  
Café Au Lait Spots

Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of KIT ligand (KITLG, MIM 184745) gene, which encodes KIT ligand protein, is responsible for FPHH.Results A novel mutation c.104A > T (p.Asn35Ile) and a recurrent mutation c.101C > T (p.Thr34Ile) in the KITLG gene with two Chinese FPHH families were identified. So far, various pathogenic gain-of-function mutations in the KITLG gene have been described, which are located in or near the conserved VTNN motif (amino acid 33–37) in exon 2 of the KITLG gene. The reported mutations are only involved in 33V, 34T, 36N, 37V but not 35N. As SIFT and Polyphen-2 softwares showed, these two mutations were both predicted to be detrimental variations. Three-dimensional protein structures modeling indicated the mutant KITLG proteins might affect KITLG affinity to its receptor c-KIT. To date, only eight KITLG mutations were associated with FPHH and no clear genotype-phenotype correlations had been well established.Conclusions We have now identified a novel mutation c.104A > T (p.Asn35Ile) of KITLG gene, which was first reported in FPHH located within the conserved 35N of the motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.

scholarly journals Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

2020 ◽  
Author(s):  
Jianbo Wang ◽  
Weisheng Li ◽  
Naihui Zhou ◽  
Jingliu Liu ◽  
Shoumin Zhang ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Protein Structures ◽  
Three Dimensional ◽  
Chinese Family ◽  
The Novel ◽  
Exon 2 ◽  
Coding Regions ◽  
Pathogenicity Prediction ◽  
Café Au Lait Spots ◽  
Genetics And Genomics

Abstract Background: Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of KIT ligand (KITLG, MIM 184745) gene is responsible for FPHH. To date, only eight KITLG mutations were reported to be associated with FPHH and no clear genotype-phenotype correlations had been well established. This study aimed to identify the causative mutations of the KITLG gene in two Chinese FPHH cases.Methods: Directly sequencing of the coding regions of KITLG was performed. The pathogenicity prediction was assessed using bioinformatics tools including SIFT, Polyphen2, and SWISS-MODEL, and further evaluated following the American College of Medical Genetics and Genomics (ACMG) guideline 2015.Results: A novel mutation c.104A>T (p.Asn35Ile) and a recurrent mutation c.101C>T (p.Thr34Ile) in KITLG were identified. As SIFT and Polyphen-2 softwares showed, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structures modeling indicated the mutant KITLG proteins might affect KITLG affinity to its receptor c-KIT. According to the ACMG guideline 2015, the novel mutation c.104A>T was ‘Likely Pathogenic’.Conclusions: So far, most of the KITLG mutations are clustered within the conserved VTNNV motif (amino acid 33-37) in exon 2. The known mutations are only involved in 33V, 34T, 36N, 37V but not 35N. We have now identified a novel mutation c.104A>T of KITLG, which was first reported in FPHH located within the conserved 35N of the motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.

scholarly journals Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

2020 ◽  
Author(s):  
Jianbo Wang ◽  
Weisheng Li ◽  
Naihui Zhou ◽  
Jingliu Liu ◽  
Shoumin Zhang ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Direct Sequencing ◽  
Three Dimensional ◽  
Chinese Family ◽  
The Novel ◽  
Exon 2 ◽  
Coding Regions ◽  
Pathogenicity Prediction ◽  
Café Au Lait Spots ◽  
Genetics And Genomics

Abstract Background: Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype-phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients.Methods: Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines.Results: The novel mutation c.104A>T (p.Asn35Ile) and the recurrent mutation c.101C>T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A>T was ‘likely pathogenic’.Conclusions: To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33-37) in exon 2. The known mutations are only involved in 33V, 34T, 36N, and 37V but not 35N. We have now identified a novel mutation in KITLG, c.104A>T, that was first reported in FPHH within the conserved 35N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.

scholarly journals Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jianbo Wang ◽  
Weisheng Li ◽  
Naihui Zhou ◽  
Jingliu Liu ◽  
Shoumin Zhang ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Direct Sequencing ◽  
Three Dimensional ◽  
Chinese Family ◽  
The Novel ◽  
Exon 2 ◽  
Coding Regions ◽  
Pathogenicity Prediction ◽  
Café Au Lait Spots ◽  
Genetics And Genomics

Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A > T (p.Asn35Ile) and the recurrent mutation c.101C > T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A > T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A > T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.

scholarly journals Ile90Met, a novel mutation in the cardiac troponin T gene for familial hypertrophic cardiomyopathy in a Chinese pedigree

2008 ◽  
Vol 90 (5) ◽  
pp. 445-450 ◽  
Author(s):  
CHAO XU ◽  
MENG WEI ◽  
BIN SU ◽  
XUE-WEI HUA ◽  
GUO-WEI ZHANG ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hypertrophic Cardiomyopathy ◽  
Linkage Analysis ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Novel Mutation ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Chinese Family ◽  
Cardiac Troponin T ◽  
Genome Wide

SummaryTo identify the disease-causing gene for a large multi-generational Chinese family affected by familial hypertrophic cardiomyopathy (FHCM), genome-wide screening was carried out in a Chinese family with FHCM using micro-satellite markers, and linkage analysis was performed using the MLINK program. The disease locus was mapped to 1q32 in this family. Screening for a mutation in the cardiac troponin T (cTnT) gene was performed by a PCR and sequencing was done with an ABI Prism 3700 sequencer. A novel C→G transition located in the ninth exon of the cTnT gene, leading to a predicted amino acid residue change from Ile to Met at codon 90, was identified in all individuals with hypertrophic cardiomyopathy (HCM). The results presented here strongly suggest that Ile90Met, a novel mutation in the cTnT gene, is causative agent of HCM in this family.

NEAT-FLEX: Predicting the conformational flexibility of amino acids using neuroevolution of augmenting topologies

2017 ◽  
Vol 15 (03) ◽  
pp. 1750009 ◽  
Author(s):  
Bruno Grisci ◽  
Márcio Dorn
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tertiary Structure ◽  
Structural Information ◽  
Protein Structures ◽  
Three Dimensional ◽  
Conformational Flexibility ◽  
Amino Acid Sequences ◽  
Conformational Search ◽  
Back Propagation Algorithm

The development of computational methods to accurately model three-dimensional protein structures from sequences of amino acid residues is becoming increasingly important to the structural biology field. This paper addresses the challenge of predicting the tertiary structure of a given amino acid sequence, which has been reported to belong to the NP-Complete class of problems. We present a new method, namely NEAT–FLEX, based on NeuroEvolution of Augmenting Topologies (NEAT) to extract structural features from (ABS) proteins that are determined experimentally. The proposed method manipulates structural information from the Protein Data Bank (PDB) and predicts the conformational flexibility (FLEX) of residues of a target amino acid sequence. This information may be used in three-dimensional structure prediction approaches as a way to reduce the conformational search space. The proposed method was tested with 24 different amino acid sequences. Evolving neural networks were compared against a traditional error back-propagation algorithm; results show that the proposed method is a powerful way to extract and represent structural information from protein molecules that are determined experimentally.

scholarly journals Protein Structure Prediction Based on Improved Genetic Algorithm

2020 ◽  
Vol 11 (9) ◽  
pp. 450-454
Author(s):  
Jiaxi Liu ◽  
Keyword(s):  
Genetic Algorithm ◽  
Protein Structure ◽  
Amino Acid ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Improved Genetic Algorithm ◽  
Research Areas

The prediction of protein three-dimensional structure from amino acid sequence has been a challenge problem in bioinformatics, owing to the many potential applications for robust protein structure prediction methods. Protein structure prediction is essential to bioscience, and its research results are important for other research areas. Methods for the prediction an才d design of protein structures have advanced dramatically. The prediction of protein structure based on average hydrophobic values is discussed and an improved genetic algorithm is proposed to solve the optimization problem of hydrophobic protein structure prediction. An adjustment operator is designed with the average hydrophobic value to prevent the overlapping of amino acid positions. Finally, some numerical experiments are conducted to verify the feasibility and effectiveness of the proposed algorithm by comparing with the traditional HNN algorithm.

scholarly journals Quantitative description and classification of protein structures by a novel robust amino acid network: interaction selective network (ISN)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shohei Konno ◽  
Takao Namiki ◽  
Koichiro Ishimori
Keyword(s):  
Amino Acid ◽  
Structural Information ◽  
Protein Structures ◽  
Quantitative Description ◽  
Three Dimensional ◽  
Network Models ◽  
Clustering Coefficient ◽  
Coarse Grained ◽  
Network Parameters ◽  
Average Vertex

Abstract To quantitatively categorize protein structures, we developed a quantitative coarse-grained model of protein structures with a novel amino acid network, the interaction selective network (ISN), characterized by the links based on interactions in both the main and side chains. We found that the ISN is a novel robust network model to show the higher classification probability in the plots of average vertex degree (k) versus average clustering coefficient (C), both of which are typical network parameters for protein structures, and successfully distinguished between “all-α” and “all-β” proteins. On the other hand, one of the typical conventional networks, the α-carbon network (CAN), was found to be less robust than the ISN, and another typical network, atomic distance network (ADN), failed to distinguish between these two protein structures. Considering that the links in the CAN and ADN are defined by the interactions only between the main chain atoms and by the distance of the closest atom pair between the two amino acid residues, respectively, we can conclude that reflecting structural information from both secondary and tertiary structures in the network parameters improves the quantitative evaluation and robustness in network models, resulting in a quantitative and more robust description of three-dimensional protein structures in the ISN.

Mutational studies of protein structures and their stabilities

1992 ◽  
Vol 25 (2) ◽  
pp. 205-250 ◽  
Author(s):  
David Shortle
Keyword(s):  
Amino Acid ◽  
Functional Role ◽  
Hydrophobic Interactions ◽  
Protein Structures ◽  
Three Dimensional ◽  
Rnase A ◽  
Side Chain ◽  
Amino Acid Side Chain ◽  
X Ray Crystallography ◽  
And Function

The fundamental relationship between structure and function has served to guide investigations into the workings of living systems at all levels - from the whole organism to individual cells on down to individual molecules. When X-ray crystallography began to reveal the three-dimensional structures of proteins like myoglobin, lysozyme and RNase A, protein chemists were well prepared to draw inferences about functional mechanisms from the precise positioning of amino acid residues they could see. The close proximity between an amino acid side chain and a chemical group on a bound ligand strongly suggests a functional role for that side chain in binding affinity and specificity. Likewise, the nearly universal finding of large clusters of hydrophobic side chains buried in the core of proteins strongly supports a major functional role of hydrophobic interactions in protein folding and stability. Even though eminently plausible hypotheses like these, grounded in the most fundamental principles of chemistry and the logic of structure–function relationships, become widely accepted and make their way into textbooks, protein chemists have felt compelled to search for ways to test them and put them on a more quantitative basis.

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