اخبار و اعلانات

 آمار

تعداد نشریات24
تعداد شماره‌ها881
تعداد مقالات7,867
تعداد مشاهده مقاله14,700,119
تعداد دریافت فایل اصل مقاله12,550,250
Rezaie, Nahid, Ghazanfari, Saeedeh Sadat, Khosravi, Teymoor, Vaghefi, Fatemeh, Oladnabi, Morteza. (1403). A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population. , 13(4), 235-246. doi: 10.22099/mbrc.2024.49847.1958
Nahid Rezaie; Saeedeh Sadat Ghazanfari; Teymoor Khosravi; Fatemeh Vaghefi; Morteza Oladnabi. "A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population". , 13, 4, 1403, 235-246. doi: 10.22099/mbrc.2024.49847.1958
Rezaie, Nahid, Ghazanfari, Saeedeh Sadat, Khosravi, Teymoor, Vaghefi, Fatemeh, Oladnabi, Morteza. (1403). 'A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population', , 13(4), pp. 235-246. doi: 10.22099/mbrc.2024.49847.1958
Rezaie, Nahid, Ghazanfari, Saeedeh Sadat, Khosravi, Teymoor, Vaghefi, Fatemeh, Oladnabi, Morteza. A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population. , 1403; 13(4): 235-246. doi: 10.22099/mbrc.2024.49847.1958

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

Molecular Biology Research Communications
دوره 13، شماره 4، 2024، صفحه 235-246    اصل مقاله (657.88 K)
نوع مقاله: Original article
شناسه دیجیتال (DOI): 10.22099/mbrc.2024.49847.1958
نویسندگان
Nahid Rezaie1؛ Saeedeh Sadat Ghazanfari2؛ Teymoor Khosravi1؛ Fatemeh Vaghefi1؛ Morteza Oladnabi* 3
1Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
2Mashhad University of Medical Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
3Gorgan Congenital Malformations Research Center, Golestan University of Medical Sciences, Gorgan, Iran
چکیده
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.
کلیدواژه‌ها
In silico analysis؛ Maple syrup urine disease؛ Mutations؛ Pathogenicity
سایر فایل های مرتبط با مقاله
مراجع
  1. Strauss KA, Carson VJ, Soltys K, Young ME, Bowser LE, Puffenberger EG, Brigatti KW, Williams KB, Robinson DL, Hendrickson C, Beiler K, Taylor CM, Haas-Givler B, Chopko S, Hailey J, Muelly ER, Shellmer DA, Radcliff Z, Rodrigues A, Loeven K, Heaps AD, Mazariegos GV, Morton DH. Branched-chain α-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes. Mol Genet Metab 2020;129: 193-206.
  2. Quental S, Vilarinho L, Martins E, Teles EL, Rodrigues E, Diogo L, Garcia P, Eusebio F, Gaspar A, Sequeira S, Amorim A, Prata MJ. Incidence of maple syrup urine disease in Portugal. Mol Genet Metab 2010;100:385-387.
  3. Morton DH, Strauss KA, Robinson DL, Puffenberger EG, Kelley RI. Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics 2002;109:999-1008.
  4. Blackburn PR, Gass JM, Vairo FPE, Farnham KM, Atwal HK, Macklin S, Klee EW. Maple syrup urine disease: mechanisms and management. Appl Clin Genet 2017;10:57-66.
  5. Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol 2014;10:723-736.
  6. Scaini G, Morais MOS, Galant LS, Vuolo F, Dall’Igna DM, Pasquali MAB, Ramos VM, Gelain DP, Moreira JCF, Schuck PF, Ferreira GC, Soriano FG, Dal-Pizzol F, Streck EL. Coadministration of branched-chain amino acids and lipopolysaccharide causes matrix metalloproteinase activation and blood–brain barrier breakdown. Mol Neurobiol 2014;50: 358-367.
  7. Gorjizadeh N, Jazayeri O, Najavand S, Alijanpour M. The genes responsible for maple syrup urine disease, Molecular pathomechanisms and causative mutations in Iranian population. J Babol Univ Med Sci 2018;20:39-48.
  8. Abiri M, Karamzadeh R, Karimipoor M, Ghadami S, Alaei MR, Dabagh Bagheri S, Bagherian H, Setoodeh A, Noori-Daloii MR, Zeinali S. Identification of six novel mutations in Iranian patients with maple syrup urine disease and their in silico analysis​. Mutat Res 2016;786:34-40.
  9. Hamamy H. Consanguineous marriages: preconception consultation in primary health care settings. J Community Genet 2012;3:185-192.
  10. Saadat M, Ansari-Lari M, Farhud DD. Short report consanguineous marriage in Iran. Ann Hum Biol 2004;31:263-269.
  11. Fattahi Z, Beheshtian M, Mohseni M, Poustchi H, Sellars E, Nezhadi SH, Amini A, Arzhangi S, Jalalvand K, Jamali P, Mohammadi Z, Davarnia B, Nikuei P, Oladnabi M, Mohammadzadeh A, Zohrehvand E, Nejatizadeh A, Shekari M, Bagherzadeh M, Shamsi-Gooshki E, Borno S, Timmermann B, Haghdoost A, Najafipour R, Khorram Khorshid HR, Kahrizi K, Malekzadeh R, Akbari MR, Najmabadi H. Iranome: A catalog of genomic variations in the Iranian population. Hum Mutat 2019;40:1968-1984.
  12. Mehrjoo Z, Fattahi Z, Beheshtian M, Mohseni M, Poustchi H, Ardalani F, Jalavand K, Arzhangi S, Mohammadi Z, Khoshbakht S, Najafi F, Nikuei P, Haddadi M, Zohrehvand E, Oladnabi M, Mohammadzadeh A, Hadi Jafari M, Akhtarkhavari T, Shamsi Gooshki E, Haghdoost A, Najafipour R, Niestroj LM, Helwing B, Gossmann Y, Toliat MR, Malekzadeh R, Nurnberg P, Kahrizi K, Najmabadi H, Nothnagel M. Distinct genetic variation and heterogeneity of the Iranian population. PLoS Genet 2019;15:e1008385.
  13. Abiri M, Saei H, Eghbali M, Karamzadeh R, Shirzadeh T, Sharifi Z, Zeinali S. Maple syrup urine disease mutation spectrum in a cohort of 40 consanguineous patients and in silico analysis of novel mutations. Metab Brain Dis 2019;34:1145-1156.
  14. Zeynalzadeh M, Tafazoli A, Aarabi A, Moghaddassian M, Ashrafzadeh F, Houshmand M, Taghehchian N, Abbaszadegan MR. Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease. J Pediatr Endocrinol Metab 2018;31:205-512.
  15. Sedaghat A, Zamani M, Jahanshahi A, Ghaderian SB, Shariati G, Saberi A, Hamid M, Aminzadeh M, Galehdari H. Frequent novel mutations are causative for maple syrup urine disease from Southwest Iran. Meta Gene 2018;16:96-104.
  16. Abiri M, Karamzadeh R, Mojbafan M, Alaei MR, Jodaki A, Safi M, Kianfar S, Bandehi Sarhaddi A, Noori-Daloii MR, Karimipoor M, Zeinali S. In silico analysis of novel mutations in maple syrup urine disease patients from Iran. Metab Brain Dis 2017;32:105-113.
  17. Alijanpour M, Jazayeri O, Soleimani Amiri S, Brosens E. Pathogenic homozygous mutations in the DBT gene (c.1174A>C) result in maple syrup urine disease in a rs12021720 carrier. Lab Med 2022;53:596-601.
  18. Mirzaee A, Pishva N, Karamizadeh Z, Kohlhase J, Purarian S, Hemmati F, Razavi M, Nasirabadi S. A classic case of maple syrup urine disease and a novel mutation in the BCKDHA gene. Iran J Neonatol 2017;8:72-74.
  19. Hayashida Y, Mitsubuchi H, Indo Y, Ohta K, Endo F, Wada Y, Mastsuda I. Deficiency of the E1β subunit in the branched-chain α-keto acid dehydrogenase complex due to a single base substitution to the intron 5, resulting in two alternatively spliced mRNAs in patient with maple syrup urine disease. Biochim Biophys Acta 1994;1225:317-325.
  20. Fang X, Zhu X, Feng Y, Bai Y, Zhao X, Liu N, Kong X. Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population. Sci Rep 2021;11:18939.
  21. Du C, Liu WJ, Yang J, Zhao SS, Liu HX. The role of branched-chain amino acids and branched-chain α-keto acid dehydrogenase kinase in metabolic disorders. Front Nutr 2022;9:932670.
  22. Jaradat SA, Al-Qa’qa K, Amayreh W, Backe PH, Al-Hawamdeh A, Karam M, Alzoubi B, Deebajah H, Al Rababah B. Molecular analysis of maple syrup urine disease in Jordanian families. Meta Gene 2016;10:81-85.
  23. Imtiaz F, Al-Mostafa A, Allam R, Ramzan K, Al-Tassan N, Tahir AI, Al-Numair NS, Al-Hamed MH, Al-Hassnan Z, Al-Owain M, Al-Zaidan H, Al-Amoudi M, Qari A, Balobaid A, Al-Sayed M. Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease. Mol Genet Metab Rep 2017; 11:17-23.
  24. Lashkarian MF, Salmani H. Identification of a novel homozygous mutation of the BCKDHB gene in an Iranian patient with maple syrup disease using next-generation sequencing. Hum Gene 2023;36:201173.
  25. AEvarsson A, Chuang JL, Wynn RM, Turley S, Chuang DT, Hol WG. Crystal structure of human branched-chain α-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease. Structure 2000;8:277-291.
آمار
تعداد مشاهده مقاله: 971
تعداد دریافت فایل اصل مقاله: 1,896


سامانه مدیریت نشریات علمی. قدرت گرفته از سیناوب