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Phenotypic Continuum of Nfu1-Related Disorders Publisher Pubmed



Kaiyrzhanov R1 ; Zaki MS2 ; Lau T1 ; Sen S3 ; Azizimalamiri R4 ; Zamani M5 ; Sayin GY6 ; Hilander T7 ; Efthymiou S1 ; Chelban V1 ; Brown R8 ; Thompson K9 ; Scarano MI10 ; Ganesh J11 Show All Authors
Authors
  1. Kaiyrzhanov R1
  2. Zaki MS2
  3. Lau T1
  4. Sen S3
  5. Azizimalamiri R4
  6. Zamani M5
  7. Sayin GY6
  8. Hilander T7
  9. Efthymiou S1
  10. Chelban V1
  11. Brown R8
  12. Thompson K9
  13. Scarano MI10
  14. Ganesh J11
  15. Koneev K12
  16. Gulacar IM6, 13
  17. Person R14
  18. Sadykova D15
  19. Maidyrov Y12
  20. Seifi T5
  21. Zadagali A16
  22. Bernard G17, 18, 19
  23. Allis K14
  24. Elloumi HZ14
  25. Lindy A14
  26. Taghiabadi E20
  27. Verma S21
  28. Logan R22
  29. Kirmse B23
  30. Bai R14
  31. Khalaf SM24
  32. Abdelhamid MS25
  33. Sedaghat A26
  34. Shariati G27, 28
  35. Issa M2
  36. Zeighami J28
  37. Elbendary HM2
  38. Brown G8
  39. Taylor RW9, 29
  40. Galehdari H5
  41. Gleeson JJ30, 31
  42. Carroll CJ7
  43. Cowan JA3
  44. Morenodeluca A32
  45. Houlden H1
  46. Maroofian R1
Show Affiliations
Authors Affiliations
  1. 1. Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, WC1N 3BG, United Kingdom
  2. 2. Human Genetics and Genome Research Division, Clinical Genetics Department, National Research Centre, Cairo, Egypt
  3. 3. Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, 43210, OH, United States
  4. 4. Department of Paediatric Neurology, Golestan, Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  5. 5. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  6. 6. Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 34098, Turkey
  7. 7. Genetics Section, Molecular and Clinical Sciences, St George's, University of London, London, United Kingdom
  8. 8. Oxford Medical Genetics Laboratories, The Churchill Hospital, Oxford, OX3 7LJ, United Kingdom
  9. 9. Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom
  10. 10. Division of Genetics, Cooper Health System, Children's Regional Hospital, Sheridan Pavilion Camden, 08103, New Jersy, United States
  11. 11. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  12. 12. Department of Neurology and Neurosurgery, Asfendiyarov Kazakh National Medical University, Almaty, 050000, Kazakhstan
  13. 13. Department of Genetics, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, 34098, Turkey
  14. 14. GeneDx, Gaithersburg, 20877, MD, United States
  15. 15. Astana Medical University, Nur-Sultan, Kazakhstan
  16. 16. L.N. Gumilyov Eurasian National University, Nur-Sultan, Kazakhstan
  17. 17. Departments of Neurology and Neurosurgery, Pediatrics and Human Genetics, McGill University, Montreal, Canada
  18. 18. Division of Medical Genetics, Department Specialized Medicine, McGill University Health Centre, Montreal, Canada
  19. 19. Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Canada
  20. 20. Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
  21. 21. Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
  22. 22. Division of Neurosciences, Children's Healthcare of Atlanta, Atlanta, GA, United States
  23. 23. Division of Genetics, University of Mississippi Medical Center, Jackson, MS, United States
  24. 24. Pediatrics Department, Assiut University, Assiut, Egypt
  25. 25. Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt
  26. 26. Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  27. 27. Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  28. 28. Narges Medical Genetics and Prenatal Diagnosis Laboratory, East Mihan Ave., Kianpars, Ahvaz, Iran
  29. 29. NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, United Kingdom
  30. 30. Department of Neurosciences, University of California, San Diego, La Jolla, 92093, CA, United States
  31. 31. Rady Children's Institute for Genomic Medicine, San Diego, 92025, CA, United States
  32. 32. Department of Radiology, Autism & Developmental Medicine Institute, Genomic Medicine Institute, Geisinger, Danville, 17822, PA, United States

Source: Annals of Clinical and Translational Neurology Published:2022


Abstract

Bi-allelic variants in Iron–Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum. © 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.