Maple syrup urine disease mutation spectrum in a cohort of 40 consanguineous patients and insilico analysis of novel mutations.

Maple syrup urine disease is the primary aminoacidopathy affecting branched-chain amino acid (BCAA) metabolism. The disease is mainly caused by the deficiency of an enzyme named branched-chained α-keto acid dehydrogenase (BCKD), which consist of four subunits (E1α, E1β, E2, and E3), and encoded by BCKDHA, BCKDHB, DBT, and DLD gene respectively. BCKD is the main enzyme in the catabolism pathway of BCAAs. Hight rate of autosomal recessive disorders is expected from consanguineous populations like Iran. In this study, we selected two sets of STR markers linked to the four genes, that mutation in which can result in MSUD disease. The patients who had a homozygous haplotype for selected markers of the genes were sequenced. In current survey, we summarized our recent molecular genetic findings to illustrate the mutation spectrum of MSUD in our country. Ten novel mutations including c.484 A > G, c.834_836dup CAC, c.357del T, and c. (343 + 1_344-1) _ (742 + 1_743-1)del in BCKDHB, c.355-356 ins 7 nt ACAAGGA, and c.703del T in BCKDHA, and c.363delCT/c.1238 T > C, c. (433 + 1_434-1) _ (939 + 1_940-1)del, c.1174 A > C, and c.85_86ins AACG have been found in DBT gene. Additionally, structural models of MSUD mutations have been performed to predict the pathogenicity of the newly identified variants.