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Maple Syrup Urine Disease Mutation Spectrum in a Cohort of 40 Consanguineous Patients and Insilico Analysis of Novel Mutations Publisher Pubmed



Abiri M1 ; Saei H1, 2 ; Eghbali M3 ; Karamzadeh R4 ; Shirzadeh T5, 6 ; Sharifi Z5, 6 ; Zeinali S5, 7
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Science, Tehran, 14494-14539, Iran
  2. 2. Student Research Committee, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  5. 5. Dr. Zeinali’s Medical Genetics Laboratory, Kawsar Human Genetics Research Center, No. 41 Majlesi St., Vali Asr St., Tehran, 1595645513, Iran
  6. 6. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  7. 7. Department of Molecular Medicine, Biotech Research Center, Pasteur Institute of Iran, Tehran, Iran

Source: Metabolic Brain Disease Published:2019


Abstract

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. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
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