In silico analysis of c.۴۹G>T (p.Gly۱۷Cys), a QDPR genemissense variant

۶R-L-erythro-۵,۶,۷,۸-tetrahydrobiopterin (BH۴) is known as an essential cofactor for some enzymes includingphenylalanine hydroxylase and genetic mutations in this cofactor may lead to hyperphenylalaninemia (HPA).Dihydropteridine reductase (DHPR) deficiency is caused by defects in the quinoid dihydropteridine reductase (QDPR)gene [۱]. QDPR gene is involved in the BH۴-recycling pathway and about ۱۵۰ variants in this gene have been recordedin PND database (available at http://www.biopku.org). The aim of this study was to predict the pathogenicity ofQDPR: c.۴۹G>T (p.Gly۱۷Cys), as a variant reported for the first time in an Iranian patient with DHPR deficiency [۲].We used ten in silico predictive tools including PANTHER PSEP (http://pantherdb.org/), PhD-SNPg(https://snps.biofold.org/phd-snpg/#), PROVEAN and SIFT (both available at: http://provean.jcvi.org/index.php),Mutation Taster (http://www.mutationtaster.org/), SNPs & GO (https://snps.biofold.org/snps-and-go/), FATHMMXF(http://fathmm.biocompute.org.uk/fathmm-xf/), I-Mutant Disease (http://gpcr.biocomp.unibo.it/cgi/predictors/IMutant۳.۰/I-Mutant۳.۰.cgi), PolyPhen-۲ (http://genetics.bwh.harvard.edu/pph۲/), CADD(https://cadd.gs.washington.edu/) in this study.The results of our analysis were as follows: PANTHER PSEP (probably damaging), PhD-SNPg (pathogenic),PROVEAN (deleterious), Mutation Taster (disease causing), SNPs & GO (disease), FATHMM-XF (pathogenic), IMutantDisease (disease), PolyPhen-۲ (probably damaging), CADD (score: ۲۶), SIFT (damaging). In conclusion, witha threshold of deleterious effects in seven or more in silico predictive tools, QDPR: c.۴۹G>T (p.Gly۱۷Cys) variantcould be accepted as a pathogenic variant. However, for its final classification, it is necessary to consider the othercriteria provided by American College of Medical Genetics and Genomics (ACMG-AMP) guidelines [۳].

کلیدواژه ها:

DHPR deficiency ، QDPR gene ، in silico analysis.