In-silico analysis of a missense mutation (Leu۳۰۹Pro) in the PYGM gene associated with Glycogen storage disease type V

Glycogen storage disease type V (also called McArdle's disease and GSDV) is a disorder ofmuscle metabolism. Muscle phosphorylase enzyme deficiency causes this disease. One of the effects ofthis disease is the inability to break down glycogen "fuel" reserves. It should be noted that McArdle'sdisease leads to reversible acute kidney failure, severe muscle damage, pain and fatigue with vigorousexercise. In most cases, the age of onset of this disease occurs in the first decade of life, but it can bedifferent. In some cases, diagnosis of the disease due to neglect of myalgia and fatigue in old age leadsto involvement of proximal muscles and continuous weakness. The diagnosis of GSDV in an individualis established by the identification of biallelic PYGM (encoding glycogen phosphorylase, muscle form).In this article, the pathogenicity of the missense mutation of the leucine amino acid at position ۳۰۹ toproline in the PYGM gene has been investigated in the PolyPhen-۲ and HOPE bases.PolyPhen-۲ is a tool that predicts the potential impact of amino acid substitutions on human proteinfunction. Regarding the Leu۳۰۹Pro amino acid mutation, according to the polyPhen-۲ results to bothHumDiv and HumVar, this mutation is indicated to be probably damaging with a score of ۱۰۰۰.Moreover HOPE is an online web service where the user can submit sequences and mutations. Basedon HOPE's survey of genomic variants, the MetaRNN score of this species is ۰.۹۸۹۸۹۰۱. It can be from۰.۰ to ۱.۰. The higher it is, the more likely it is to be pathogenic, so the mutation is likely to damage theprotein.In conclusion, it is likely that this missense mutation in the PYGM gene is pathogenic and possiblydamaging.

کلیدواژه ها:

McArdle disease ، GSDV ، PYGM