In silico analysis of five missense mutations in CYP1B1 gene in Pakistani families affected with primary congenital glaucoma

2017 ◽  
Vol 38 (2) ◽  
pp. 807-814 ◽  
Author(s):  
Sabika Firasat ◽  
Haiba Kaul ◽  
Usman Ali Ashfaq ◽  
Sobia Idrees
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Congenital Glaucoma ◽  
Missense Mutations ◽  
Primary Congenital Glaucoma ◽  
Cyp1b1 Gene ◽  
Pakistani Families ◽  
Silico Analysis

CYP1B1 and MYOC variants in neonatal-onset versus infantile-onset primary congenital glaucoma

2021 ◽  
pp. bjophthalmol-2020-318563
Author(s):  
Sushmita Kaushik ◽  
Manni Luthra-Guptasarma ◽  
Dimple Prasher ◽  
Deepika Dhingra ◽  
Nirbhai Singh ◽  
...  
Keyword(s):  
In Silico ◽  
Severe Disease ◽  
In Silico Analysis ◽  
Allelic Frequency ◽  
Congenital Glaucoma ◽  
Primary Congenital Glaucoma ◽  
Pathogenic Variants ◽  
Neonatal Onset ◽  
Silico Analysis

ObjectiveTo compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG).MethodsThis prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups.ResultsBabies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls.ConclusionsPatients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG.

scholarly journals Functional in silico analysis of missense mutations in the MSH6 gene

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
Katarzyna Gajdel ◽  
Grzegorz Kurzawski
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
Msh6 Gene ◽  
Silico Analysis

scholarly journals In silico analysis of missense mutations in exons 1–5 of the F9 gene that cause hemophilia B

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lennon Meléndez-Aranda ◽  
Ana Rebeca Jaloma-Cruz ◽  
Nina Pastor ◽  
Marina María de Jesús Romero-Prado
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Hemophilia B ◽  
Missense Mutations ◽  
Silico Analysis

Hyperphenylalaninemia in the Czech Republic: Genotype–phenotype correlations and in silico analysis of novel missense mutations

2013 ◽  
Vol 419 ◽  
pp. 1-10 ◽  
Author(s):  
Kamila Réblová ◽  
Zuzana Hrubá ◽  
Dagmar Procházková ◽  
Renata Pazdírková ◽  
Slávka Pouchlá ◽  
...  
Keyword(s):  
Czech Republic ◽  
In Silico ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
The Czech Republic ◽  
Silico Analysis

scholarly journals A Genotype-Phenotype Correlation of Haemophilia a in Victorian Patients with a Description of Novel Mutations

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2498-2498
Author(s):  
Shreerang Sirdesai ◽  
Kerryn Weekes ◽  
Asif Alam ◽  
Huyen A Tran ◽  
Christopher Barnes ◽  
...  
Keyword(s):  
In Silico ◽  
Family Members ◽  
In Silico Analysis ◽  
Clinical Severity ◽  
Missense Mutations ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Mild Phenotype ◽  
Genotype Phenotype Correlation ◽  
Silico Analysis

Abstract Aim: Hemophilia A (HA) is caused by abnormalities in the Factor VIII gene. Certain abnormalities correlate with disease severity. Here, we report the genotype-phenotype correlation for all Victorian HA patients. Methods: Using the Australian Bleeding Disorders Registry, Victorian HA patients were identified. All genetic testing was conducted at Southern Health. The testing algorithm is summarized in Figure 1. Mutations were compared with the list of known Factor 8 mutations on the Champ and EAHAD F8 Variant Databases. A PubMed search was undertaken for any mutations not on either database. If this too was unrevealing, the mutation was designated novel. In-silico analysis was conducted on all novel mutations using three open-access, online prediction tools: a) Mutation Taster; b) Poly-Phen 2; c) Human Splice Site Predictor. Results: 318 patients with matched clinical and genetic records were identified. 275 had known FVIII mutations and 36 novel FVIII mutations were discovered. Eight patients (3%) had no mutations identified. (Table 1) In severe HA the intron-22 inversion was the most common mutation (47/122, 38%). Missense mutations predominated in mild and moderate HA. Inhibitors were present in 44/318 patients, the majority of whom had 26/44 (59%) severe HA. 20/36 novel mutations (55%) were associated with severe HA, 12/36 (33%) with mild HA and 4/36 (11%) with a moderate HA. Novel mutations associated with non-severe phenotypes were mostly missense mutations (15/16); More diversity was seen in the novel mutations causing a severe HA with a fairly even distribution of mutations: missense (7/20), nonsense (4/20) and small deletions and insertions (8/20). One large deletion involving a 6.5kb region of exon 26, as well as one duplication of exons 7 to 9 - was seen in the severe group. In-silico analysis predicted that all novel severe HA mutations were likely to be pathogenic.Inhibitors were seen in 7 patients with novel mutations. Of the 36 novel mutations we described, 9/36 (25%) were seen in other family members - often female carriers. All 9 mutations caused a severe phenotype which is not unexpected given that the screening and testing of family members would be unlikely to take place in patients who have a mild phenotype and rarely require supportive medical care Conclusion: This study adds 36 novel mutations to the currently known FVIII haemophilic mutations. It also confirms that the frequency and correlative clinical severity of known genetic mutations in the Victorian HA cohort is similar to that described internationally. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genetics A Comprehensive In Silico Analysis of Deleterious SNPs of Paraplegin Protein Associated with Hereditary Spastic Paraplegia through Mitochondrial Dysfunction

2020 ◽  
Vol 2 (2) ◽  
pp. 1-14
Author(s):  
Ammara Akhtar ◽  
Sobia Nazir Choudhry ◽  
Rana Muhammad Mateen ◽  
Mureed Hussain
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
In Silico ◽  
Mitochondrial Protein ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
Spastic Paraplegia ◽  
Bioinformatic Tools ◽  
Pathogenic Variants ◽  
Structural And Functional Properties ◽  
Silico Analysis

Hereditary spastic paraplegia (HSP) is a heterogenous neurological disorder primarily associated with progressive spasticity. Paraplegin is a mitochondrial protein and mutations in this protein can lead to HSP. In this study, in silico analysis was carried out to identify the pathogenic variants of SPG7 (paraplegin protein). To find novel pathogenic mutations, missense and splicing variants were collected from gnomAD database and passed through a detailed and stringent analysis with the help of a variety of bioinformatic tools. The list of mutations was examined and compared in ClinVar. Altogether, 14 missense mutations and 18 splicing mutations were obtained and these mutations were predicted to have the potential of disrupting the normal structural and functional properties of paraplegin protein.

scholarly journals In Silico Analysis of Missense Mutations in LPAR6 Reveals Abnormal Phospholipid Signaling Pathway Leading to Hypotrichosis

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104756 ◽  
Author(s):  
Syed Irfan Raza ◽  
Dost Muhammad ◽  
Abid Jan ◽  
Raja Hussain Ali ◽  
Mubashir Hassan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
In Silico ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
Phospholipid Signaling ◽  
Silico Analysis

In Silico Analysis of NF2 Gene Missense Mutations in Neurofibromatosis Type 2

2015 ◽  
Vol 36 (5) ◽  
pp. 908-914 ◽  
Author(s):  
Thomas E. Heineman ◽  
D. Gareth R. Evans ◽  
Fabien Campagne ◽  
Samuel H. Selesnick
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Missense Mutations ◽  
Nf2 Gene ◽  
Silico Analysis

scholarly journals In Silico Analysis of Missense Mutations as a First Step in Functional Studies: Examples from Two Sphingolipidoses

2018 ◽  
Vol 19 (11) ◽  
pp. 3409 ◽  
Author(s):  
Ana Duarte ◽  
Diogo Ribeiro ◽  
Luciana Moreira ◽  
Olga Amaral
Keyword(s):  
Amino Acid ◽  
Protein Level ◽  
In Silico ◽  
In Silico Analysis ◽  
Amino Acid Substitutions ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Functional Studies ◽  
Analysis System ◽  
Silico Analysis

In order to delineate a better approach to functional studies, we have selected 23 missense mutations distributed in different domains of two lysosomal enzymes, to be studied by in silico analysis. In silico analysis of mutations relies on computational modeling to predict their effects. Various computational platforms are currently available to check the probable causality of mutations encountered in patients at the protein and at the RNA levels. In this work we used four different platforms freely available online (Protein Variation Effect Analyzer- PROVEAN, PolyPhen-2, Swiss-model Expert Protein Analysis System—ExPASy, and SNAP2) to check amino acid substitutions and their effect at the protein level. The existence of functional studies, regarding the amino acid substitutions, led to the selection of the distinct protein mutants. Functional data were used to compare the results obtained with different bioinformatics tools. With the advent of next-generation sequencing, it is not feasible to carry out functional tests in all the variants detected. In silico analysis seems to be useful for the delineation of which mutants are worth studying through functional studies. Therefore, prediction of the mutation impact at the protein level, applying computational analysis, confers the means to rapidly provide a prognosis value to genotyping results, making it potentially valuable for patient care as well as research purposes. The present work points to the need to carry out functional studies in mutations that might look neutral. Moreover, it should be noted that single nucleotide polymorphisms (SNPs), occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here.

Corrigendum to “Hyperphenylalaninemia in the Czech Republic: genotype–phenotype correlations and in silico analysis of novel missense mutations” [Clin Chim Acta 419C: (2013) 1–10]

2013 ◽  
Vol 426 ◽  
pp. 157 ◽  
Author(s):  
Kamila Réblová ◽  
Zuzana Hrubá ◽  
Dagmar Procházková ◽  
Renata Pazdírková ◽  
Slávka Pouchlá ◽  
...  
Keyword(s):  
Czech Republic ◽  
In Silico ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
The Czech Republic ◽  
Silico Analysis
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