Wilms’ tumor (WT) is an embryonic tumor of kidney that belongs to paediatric age group. The etiopathology is highly complex due to interaction between genetic
and epigenetic factors. The genetic heterogeneity of methylene tetrahydrofolate reductase (MTHFR) gene polymorphism increase “risk factor” of the disease.
The present study has been designed to identify new gene variants single nucleotide polymorphism (SNP) of MTHFR using Sanger’s sequencing and decode the
nucleotide sequences into corresponding amino acids to understand the translational events. Further, allele refractive mutation system with polymerase chain
reaction (ARMS- PCR) was also used to confirm mutations (frequency) in the cases of WT and compare with age matched controls. Present findings reveal
that genetic heterozygosity was observed in 20% cases of WT by substitution of nucleotide cytosine in to thymidine (C→T) followed by change of amino acid
alanine is replaced by valine due to missense mutation. DNA sequencing data varies in different cases of WT that includes - first case shows four new SNPs -1)
nucleotide cytosine is substitute by thymidine (C→T) followed by change in amino acid alanine is replaced by valine, 2) thymidine change into adenine (T→A)
results in isoleucine→asparagine, 3) cytosine is substitute by adenine (C→A) results in isoleucine →asparagine, and 4) thymidine is substitute by cytosine
(T→C), where phenylalanine →serine. Similarly, Second and third case of WT again showing the missense mutation, where the nucleotide cytosine is substitute
by thymidine (C→T) followed by alanine→valine and thymidine into adenine (T→A) followed by change in isoleucine→asparagine, respectively. Based on
bioinformatics analysis, the 3D structure predicted that the mutation in MTHFR gene modulate the functional activity of ligand binding sites either with protein or
methotrexate. Collective findings of PCR and DNA sequencing suggests that these new gene variants which has not been reported earlier might have interfere
in folate - metabolism during DNA methylation and increase genetic susceptibility and “risk factor” in WT cases.