# A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population

## TL;DR

This study explores the genetic mutations causing maple syrup urine disease in Iran, using computational tools to understand their impact on protein structure and function.

## Contribution

The study identifies a potential pathogenic variant specific to the Iranian population and provides insights into MSUD-related protein interactions.

## Key findings

- A potential pathogenic variant (c.554C>T) was identified in the Iranian population.
- In silico analysis revealed structural and functional impacts of MSUD-related mutations.
- Protein-protein interaction networks involving MSUD genes were elucidated.

## Abstract

Maple syrup urine disease (MSUD) represents an infrequent metabolic disease precipitated by an insufficiency of the enzymatic complex known as branched-chain alpha-keto acid dehydrogenase. MSUD can be classified as classic (severe), intermediate, or intermittent based on the severity of the condition. The disease is associated with mutations in several genes, including BCKDHA, BCKDHB, DBT, and DLD. This study aimed to investigate the genetic landscape of MSUD in Iranian patients and explore the clinical implications of identified gene variants. A comprehensive analysis was conducted using various molecular techniques and bioinformatics tools to predict protein stability, pathogenicity, amino acid conservation, and secondary/tertiary structure. The in silico analysis highlighted high-risk pathogenic variants and provided insights into their potential impact on protein structure and function. Furthermore, the predicted 3D structures of wild-type and mutant proteins elucidated structural differences. Protein-protein interaction analysis shed light on the network of interactions involving MSUD-related proteins. The Iranome database uncovered a potential pathogenic variant (c.554C>T) in the Persian population. This research contributes to a better understanding of MSUD genetics in the Iranian population and outlines potential avenues for further clinical investigations. The findings have implications for genetic testing, prognosis, and genetic counseling in affected families.