Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
In Silico Analysis of Novel Mutations in Maple Syrup Urine Disease Patients From Iran Publisher Pubmed



Abiri M1, 2 ; Karamzadeh R3, 4 ; Mojbafan M1, 2 ; Alaei MR5, 6 ; Jodaki A7 ; Safi M8 ; Kianfar S7 ; Bandehi Sarhaddi A7, 9 ; Nooridaloii MR1 ; Karimipoor M2 ; Zeinali S2, 7
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Pasteur St, Tehran, Iran
  2. 2. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  4. 4. Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  5. 5. Pediatric Endocrinology and Metabolism, Mofid Children’s Hospital, Tehran, Iran
  6. 6. Pediatric Endocrinology and Metabolism, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Dr. Zeinali’s Medical Genetics Laboratory, Kawsar Human Genetics Research Center, No. 41 Majlesi St., Vali Asr St, Tehran, 1595645513, Iran
  8. 8. Path biology lab, Pars hospital, Tehran, Iran
  9. 9. Science and Research Branch, Islamic Azad University, Tehran, Iran

Source: Metabolic Brain Disease Published:2017


Abstract

Maple Syrup Urine Disease (MSUD) is a rare autosomal recessive disorder of branched-chain amino acid (BCAA) metabolism. The disease is mainly caused by mutations either in the BCKDHA, BCKDHB, DBT or DLD genes encoding components of the E1α, E1β, E2 and E3 subunits of branched-chain α-keto acid dehydrogenase complex (BCKDC), respectively. BCKDC is a mitochondrial enzyme which is responsible for the normal breakdown of BCAA. The rate of consanguineous marriage in Iran is 38.6 %, so the prevalence of autosomal recessive disorders is higher in comparison to other countries. Consanguinity increases the chance of the presence of pathogenic mutations in a homoallelic state. This phenomenon has made homozygosity mapping a powerful tool for finding the probable causative gene in heterogeneous disorders like IEM (Inborn Errors of Metabolism). In this study, two sets of multiplex polymorphic STR (Short Tandem Repeat) markers linked to the above-mentioned genes were selected to identify the probable pathogenic gene in the studied families. The families who showed a homozygous haplotype for the STR markers of the BCKDHB gene were subsequently sequenced. Four novel mutations including c.633 + 1G > A, c.988G > A, c.833_834insCAC, and a homozygous deletion of whole exon 3 c. (274 + 1_275–1) _(343 + 1_344–1), as well as one recently reported (c. 508G > T) mutation have been identified. Interestingly, three families shared a common haplotype structure along with the c. 508G > T mutation. Also, four other families revealed another similar haplotype with c.988G > A mutation. Founder effect can be a suggestive mechanism for the disease. Additionally, structural models of MSUD mutations have been performed to predict the pathogenesis of the newly identified variants. © 2016, Springer Science+Business Media New York.
Related Docs
View other Related Docs
1. Maple Syrup Urine Disease Mutation Spectrum in a Cohort of 40 Consanguineous Patients and Insilico Analysis of Novel Mutations, Metabolic Brain Disease (2019)
2. Identification of Six Novel Mutations in Iranian Patients With Maple Syrup Urine Disease and Their in Silico Analysis, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis (2016)
3. Co-Existence of Phenylketonuria Either With Maple Syrup Urine Disease or Sandhoff Disease in Two Patients From Iran: Emphasizing the Role of Consanguinity, Journal of Pediatric Endocrinology and Metabolism (2016)
4. Autozygosity Mapping of Methylmalonic Acidemia Associated Genes by Short Tandem Repeat Markers Facilitates the Identification of Five Novel Mutations in an Iranian Patient Cohort, Metabolic Brain Disease (2018)
5. Beta Thalassemia in 31,734 Cases With Hbb Gene Mutations: Pathogenic and Structural Analysis of the Common Mutations; Iran As the Crossroads of the Middle East, Blood Reviews (2016)
6. Molecular Genetics of a Cohort of 635 Cases of Phenylketonuria in a Consanguineous Population, Journal of Inherited Metabolic Disease (2018)
7. Rational Design of Anti-Angiogenic Peptides to Inhibit Vegf/Vegfr2 Interactions for Cancer Therapeutics, Anti-Cancer Agents in Medicinal Chemistry (2022)
8. Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b), Orphanet Journal of Rare Diseases (2020)
Experts (# of related papers)
View all Related Experts
Massoud Amanlou (5)
Arya Sotoudeh (4)
Other Related Docs
9. Identification of a Novel Stop Loss Mutation in P2rx2 Gene in an Iranian Family With Autosomal Nonsyndromic Hearing Loss, Iranian Biomedical Journal (2021)
10. Novel Stag3 Variant Associated With Primary Ovarian Insufficiency and Non-Obstructive Azoospermia in an Iranian Consanguineous Family, Gene (2022)
11. Deletion of Loop Fragment Adjacent to Active Site Diminishes the Stability and Activity of Exo-Inulinase, International Journal of Biological Macromolecules (2016)
12. A Novel Mutation in the Pax3 Gene Causes Waardenburg Syndrome Type I in an Iranian Family, International Journal of Pediatric Otorhinolaryngology (2015)
13. Genetic Homozygosity in a Diverse Population: An Experience of Long Qt Syndrome, International Journal of Cardiology (2020)
14. Display of B. Pumilus Chitinase on the Surface of B. Subtilis Spore As a Potential Biopesticide, Pesticide Biochemistry and Physiology (2017)
15. Gene-Targeted Next Generation Sequencing Identifies Pnpla1 Mutations in Patients With a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis: The Impact of Consanguinity, Journal of Investigative Dermatology (2017)
16. Brown-Vialetto-Van Laere Syndrome and Fazio-Londe Syndrome: A Novel Mutation and in Silico Analyses, Journal of Clinical Neuroscience (2020)
17. Molecular Characterization of Qdpr Gene in Iranian Families With Bh4 Deficiency: Reporting Novel and Recurrent Mutations, JIMD Reports (2015)
18. Optimized Protocol for Soluble Prokaryotic Expression, Purification and Structural Analysis of Human Placenta Specific-1(Plac1), Protein Expression and Purification (2017)
19. Azoridactase Enzyme Engineering to Induce Structural Changes in the Active Site and Improve Its Affinity for Azo Dyes, Journal of Knowledge and Health in Basic Medical Sciences (2024)
20. The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes, Gut Pathogens (2021)
21. The Importance of the Non-Active Site and Non-Periodical Structure Located Histidine Residue Respect to the Structure and Function of Exo-Inulinase, International Journal of Biological Macromolecules (2017)
22. Functional Characterization and Development of Novel Human Kinase Insert Domain Receptor Chimeric Antigen Receptor T-Cells for Immunotherapy of Non-Small Cell Lung Cancer, European Journal of Pharmaceutical Sciences (2023)
23. Mutational Analysis of Cyp1b1 Gene in Iranian Pedigrees With Glaucoma Reveals Known and Novel Mutations, International Ophthalmology (2021)
24. A Novel Pathogenic Variant in the Mitf Gene Segregating With a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred, Molecular Syndromology (2017)
25. Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type Vi and Fanconi−Bickel Syndrome, Frontiers in Genetics (2021)
26. Mutation Spectra of the Itgb2 Gene in Iranian Families With Leukocyte Adhesion Deficiency Type 1, Human Immunology (2016)
27. Detection of Variants in Dystroglycanopathy-Associated Genes Through the Application of Targeted Whole-Exome Sequencing Analysis to a Large Cohort of Patients With Unexplained Limb-Girdle Muscle Weakness, Skeletal Muscle (2018)
28. A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in Tlrs Signaling Pathway Genes, International Journal of Molecular and Cellular Medicine (2016)
29. Identification of a Novel Frameshift Mutation in the Tecta Gene in an Iranian Family With Autosomal Nonsyndromic Hearing Loss, Acta Medica Iranica (2021)
30. A Novel Pathogenic Variant in the Fzd6 Gene Causes Recessive Nail Dysplasia in a Large Iranian Kindred, Journal of Dermatological Science (2017)
31. Clinical, Immunologic, and Genetic Spectrum of 696 Patients With Combined Immunodeficiency, Journal of Allergy and Clinical Immunology (2018)
32. Vegfr2 Mimicking Peptide Inhibits the Proliferation of Human Umbilical Vein Endothelial Cells (Huvecs) by Blocking Vegf, Anti-Cancer Agents in Medicinal Chemistry (2023)
33. Autosomal Dominant Deficiency of the Interleukin-17F in Recurrent Aphthous Stomatitis: Possible Novel Mutation in a New Entity, Gene (2018)
34. Novel Disease-Causing Variants in a Cohort of Iranian Patients With Metachromatic Leukodystrophy and in Silico Analysis of Their Pathogenicity, Clinical Neurology and Neurosurgery (2021)
35. Cloning, High-Level Gene Expression and Bioinformatics Analysis of Sp15 and Leif From Leishmania Major and Iranian Phlebotomus Papatasi Saliva As Single and Novel Fusion Proteins: A Potential Vaccine Candidate Against Leishmaniasis, Transactions of the Royal Society of Tropical Medicine and Hygiene (2021)
36. Identification of a Novel Mutation in the St14 Gene in an Iranian Family With Ichthyosis and Hypotrichosis, Dermatology Online Journal (2019)
37. Whole Exome Sequencing Reveals a Xpnpep3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient, Iranian Biomedical Journal (2020)
38. The Outward Shift of Clarithromycin Binding to the Ribosome in Mutant Helicobacter Pylori Strains, Helicobacter (2020)
39. Novel Variants Broaden the Phenotypic Spectrum of Plekhg5-Associated Neuropathies, European Journal of Neurology (2021)
40. Once in a Blue Moon, a Very Rare Coexistence of Glutaric Acidemia Type I and Mucopolysaccharidosis Type Iiib in a Patient, Iranian Biomedical Journal (2020)
41. Insights Into the Molecular-Level Details of Betaine Interactions With Laccase Under Various Thermal Conditions, Journal of Molecular Liquids (2021)
42. The Spectrum of Atm Gene Mutations in Iranian Patients With Ataxia-Telangiectasia, Pediatric Allergy and Immunology (2021)
43. Identification of Uba1 As the Causative Gene of an X-Linked Non-Kennedy Spinal–Bulbar Muscular Atrophy, European Journal of Neurology (2022)
44. Targeting Caveolin-1 and Claudin-5 With Ay9944, Improve Blood–Brain Barrier Permeability; Computational Simulation and Experimental Study, Cellular and Molecular Neurobiology (2022)
45. A Novel Compound Heterozygote Mutation in the Arsb Gene in a Patient With Maroteaux-Lamy Syndrome and Its Insilico Evaluation, Meta Gene (2018)
46. A Rare Form of Limb Girdle Muscular Dystrophy (Type 2E) Seen in an Iranian Family Detected by Autozygosity Mapping, Journal of Neurogenetics (2016)
47. Autosomal Recessive Congenital Ichthyosis: Cers3 Mutations Identified by a Next Generation Sequencing Panel Targeting Ichthyosis Genes, European Journal of Human Genetics (2017)
48. Peptide-Membrane Docking and Molecular Dynamic Simulation of in Silico Detected Antimicrobial Peptides From Portulaca Oleracea’S Transcriptome, Probiotics and Antimicrobial Proteins (2024)
49. Mutation in Twinkle in a Large Iranian Family With Progressive External Ophthalmoplegia, Myopathy, Dysphagia and Dysphonia, and Behavior Change, Archives of Iranian Medicine (2016)
50. A Novel Autosomal Recessive Gjb2-Associated Disorder: Ichthyosis Follicularis, Bilateral Severe Sensorineural Hearing Loss, and Punctate Palmoplantar Keratoderma, Human Mutation (2019)