Prediction of Pathogenicity of a Single Nucleotide Polymorphism (rs۲۱۳۳۷۸۵۶۹۳) in human CDKN۱C gene Associated with Wilms Tumor

Wilms tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer.Although healthy children develop WT, it is more common in children with cancer predispositiondisorders like Denys-Drash syndrome, WAGR syndrome, or Beckwith-Wiedemann syndrome (BWS).Patients with BWS are at an approximately ۸۰۰-fold increased relative risk of developing WT.Beckwith-Wiedemann Syndrome is a rare genetic disorder that causes macroglossia, hemihyperplasia,omphalocele, neonatal hypoglycemia, macrosomia, embryonal tumors (such as Wilms tumor),visceromegaly, adrenocortical cytomegaly, kidney abnormalities, and ear creases / posterior helical earpits. Pathogenic variants of heterozygous maternal Cyclin-dependent kinase inhibitor ۱C (CDKN۱C)are one of the five molecular mechanisms found in individuals with BWS. This study aims to assess thepathogenicity of a missense mutation in CDKN۱C (rs۲۱۳۳۷۸۵۶۹۳). This mutation changes thetryptophan at position ۷۹ to cysteine (W۷۹C). This assessment has been analyzed using severalbioinformatics tools including polyphen-۲, I-Mutant ۲.۰, and SIFT. Results showed that rs۲۱۳۳۷۸۵۶۹۳affected the protein function with a score of ۰.۰ by the SIFT. Polyphen-۲ web-based tool analysisindicated that this mutation was likely deleterious and is predicted to be probably damaging with PSICindex score of ۱.۰۰. Additionally, I-Mutant suggested that this missense mutation will decrease thestability of the CDKN۱C protein. In conclusion, W۷۹C might have pathogenic effects on the CDKN۱Cprotein. Further experimental research is required to validate this hypothesis.

کلیدواژه ها:

CDKN۱C gene ، Beckwith-Wiedemann syndrome(BWS) ، Wilms tumor(WT) ، rs۲۱۳۳۷۸۵۶۹۳ ، SNP