Frequent novel mutations are causative for maple syrup urine disease from Southwest Iran

Abstract Background Maple syrup urine disease (MSUD) is a group of neuro-metabolic disorders with autosomal recessive inheritance. MSUD is genetically caused by disruptive mutations in three genes including the BCKDHA , the BCKDHB , and the DBT . Dysfunction of one of these genes leads to the accumulation of branched-chain amino acids (BCAA) and their branched-chain-keto acids (BCKA) in the body and finally to progressive neurological and developmental disturbance. Methods Here, we applied Sanger sequencing of entire exons of the BCKDHA , the BCKDHB , and the DBT genes for 23 patients were diagnosed with MSUD from Southwest Iran. Detected changes were then subjected for in silico analysis to predict their pathogenesis. Results We found eight single nucleotide substitutions (g.13185C > A, g.16666C > T, g.25206G > A, g.25254C > A in BCKDHA , g.62247A > G, g.62259C > T and g.166525G > A in BCKDHB and g.43331A > G in DBT ) and two single nucleotide deletions (g.13212_13212delT and g.27078_27078delC in BCKDHA ). According to the designed in silico analyses, we suggest that the g.16666C > T, the g.25206G > A, the g.25254C > A, the g.62247A > G, the g.62259C > T, the g.166525G > A, the g.13212_13212delT, and the g.27078_27078delC are probably damaging. On the other hand, the g.13185C > A and the g.43331A > G changes might be neutral variations. Conclusion All variations somewhat can affect the structure, the function and the stability of gene products. The results obtained from this study could be useful to facilitate clinical diagnosis and screening of MSUD patients and partly for at-risk carriers and prenatal detection in the population of southwest of Iran.