In-silico analysis of SHOX Gene for Following Pathogenicity Single- Nucleotide Polymorphisms (SNPs) in Patients with Short Stature Deficiencies

Backgrounds: The SHOX gene (short-stature homeobox) is in pseudo-autosomal region۱(PAR۱), located on Xp۲۲.۳۳ and Yp۱۱.۳۲ chromosomes, encodes a transcription factor thatregulates the differentiation and apoptosis of chondrocytes in the epiphyseal growth plates.SHOX mutations are related to different dysplasia, including, Leri- Weill dyschondrosteosis(LWD), Langer mesomelic dysplasia (LMD), and idiopathic short stature. Also, the loss of the Xchromosome causes a sex- chromosome aneuploidy deficiency called Turner syndrome withsigns of short stature in women.Materials and Methods: This gene has ۸ exons, and the seventh exon is a hotspot one with ۶۹missense variants. These SNPs (single nucleotide polymorphisms) were analyzed forpathogenicity in SIFT (sorting intolerant from tolerant), Polyphen-۲, I-Mutant, PANTHER,PROVEAN.Results: All ۶۹ SNPs are analyzed in SIFT server at first, and only ۱۱ ones are “AFFECTED”,thereby these selected variants are considered in four other servers. In polyphen-۲ five SNPs of۱۱ variants are more severe (score:۱.۰۰۰, sensivity:۰.۰۰, and specificity:۱.۰۰) with prediction“probably damaging”, resulting in I-Mutant with ۵ more pathogenic variants in negative DDG(about ۰.۸۰-۱.۱۶), in PROVEAN also five SNPs with a high degree of “Deleterious” (score:from -۴.۱۷۸ to -۵.۴۵۴), finally for PANTHER, which all of ۱۱ considered variants shown adegree of conservation۷۵۰ million years with the prediction of “probably damaging”.Conclusion: Actually, between all of these considered pathogens SNPs with rs۱۲۲۱۳۵۶۸۶۹ andrs۱۳۱۹۲۱۰۴۱۱ could be the most pathogens related to the disease that may be as a point in thetreatment of disorders with these variants in the future.

Keywords:

SHOX gene , SNP , Mutation , Variant , Pathogenicity