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Molecular Characterization of a Large Cohort of Mucopolysaccharidosis Patients: Iran Mucopolysaccharidosis Re-Diagnosis Study (Impression) Publisher Pubmed



Ghaffari SR1, 2, 3 ; Rafati M1, 2 ; Shadnoush M4 ; Pourbabaee S5 ; Aghighi M6 ; Mirab Samiee S7, 8 ; Kermanchi J6 ; Alaei MR9 ; Salehpour S9 ; Amirkashani D10 ; Setoodeh A11 ; Sarkhail P12 ; Badv RS13 ; Aminzadeh M14 Show All Authors
Authors
  1. Ghaffari SR1, 2, 3
  2. Rafati M1, 2
  3. Shadnoush M4
  4. Pourbabaee S5
  5. Aghighi M6
  6. Mirab Samiee S7, 8
  7. Kermanchi J6
  8. Alaei MR9
  9. Salehpour S9
  10. Amirkashani D10
  11. Setoodeh A11
  12. Sarkhail P12
  13. Badv RS13
  14. Aminzadeh M14
  15. Shiva S15
  16. Eshraghi P16
  17. Moravej H17
  18. Hashemipour M18
  19. Rostampour N19
  20. Hamidieh A20
  21. Shamsian BS21
  22. Shams S22
  23. Zamanfar D23
  24. Ebrahimi A15
  25. Otadi A24
  26. Tara SZ25
  27. Barati Z1, 2
  28. Fakhri L1, 2
  29. Hoseini A2
  30. Amiri H2
  31. Ramandi S2
  32. Mostofinezhad N2
  33. Kani ZP26
  34. Mohammadyari E26
  35. Khosravi M26
  36. Saadati M27
  37. Hoseininasab F2
  38. Khorram Khorshid HR1
  39. Modaberisaber Y1
Show Affiliations
Authors Affiliations
  1. 1. Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  2. 2. Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
  3. 3. Department of Genomics, Gene Clinic, Tehran, Iran
  4. 4. Department of Clinical Nutrition, Faculty of Nutrition & Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran
  6. 6. Transplantation and Diseases Administration, Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran
  7. 7. Food and Drug Laboratory Research Center, Ministry of Health and Medical Education, Tehran, Iran
  8. 8. General Reference Health Laboratory, Ministry of Health and Medical Education, Tehran, Iran
  9. 9. Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  10. 10. Division of Endocrinology and Metabolism, Ali-Asghar Children's Hospital, Iran University of Medical Sciences, Tehran, Iran
  11. 11. Children's Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Personalized Medicine and Genometabolomics Research Center, Hope Generation Foundation, Tehran, Iran
  13. 13. Department of Pediatrics, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  14. 14. Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Khuzestan, Ahvaz, Iran
  15. 15. Pediatric Health Research Center, Tabriz University of Medical Sciences, East Azerbaijan, Tabriz, Iran
  16. 16. Department of Pediatrics, Mashhad University of Medical Sciences, Khorasan Razavi, Mashhad, Iran
  17. 17. Neonatal Research Center, Shiraz University of Medical Science, Fars, Shiraz, Iran
  18. 18. Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Isfahan, Iran
  19. 19. Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences Isfahan, Isfahan, Isfahan, Iran
  20. 20. Pediatric Cell and Gene Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran
  21. 21. Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  22. 22. Department of Pathology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  23. 23. Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  24. 24. The University of British Columbia, Faculty of Science, Vancouver, BC, Canada
  25. 25. Pediatric Endocrinology Department, The Children's Hospital of Philadelphia, Philadelphia, PA, United States
  26. 26. Islamic Azad University Tehran Medical Sciences, Tehran, Tehran, Iran
  27. 27. Islamic Azad University Tehran North Branch, Tehran, Tehran, Iran

Source: Human Mutation Published:2022


Abstract

Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through reanalysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, 90 harbored novel variants, and 9 had copy number variations. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50]). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants. © 2022 Wiley Periodicals LLC.
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