Annals of Clinical and Translational Neurology (Dec 2022)
Phenotypic continuum of NFU1‐related disorders
- Rauan Kaiyrzhanov,
- Maha S. Zaki,
- Tracy Lau,
- Sambuddha Sen,
- Reza Azizimalamiri,
- Mina Zamani,
- Gözde Yeşil Sayin,
- Taru Hilander,
- Stephanie Efthymiou,
- Viorica Chelban,
- Ruth Brown,
- Kyle Thompson,
- Maria Irene Scarano,
- Jaya Ganesh,
- Kairgali Koneev,
- Ismail Musab Gülaçar,
- Richard Person,
- Dinara Sadykova,
- Yerdan Maidyrov,
- Tahereh Seifi,
- Aizhan Zadagali,
- Geneviève Bernard,
- Katrina Allis,
- Houda Zghal Elloumi,
- Amanda Lindy,
- Ehsan Taghiabadi,
- Sumit Verma,
- Rachel Logan,
- Brian Kirmse,
- Renkui Bai,
- Shaimaa M. Khalaf,
- Mohamed S. Abdel‐Hamid,
- Alireza Sedaghat,
- Gholamreza Shariati,
- Mahmoud Issa,
- Jawaher Zeighami,
- Hasnaa M. Elbendary,
- Garry Brown,
- Robert W. Taylor,
- Hamid Galehdari,
- Joseph J. Gleeson,
- Christopher J. Carroll,
- James A. Cowan,
- Andres Moreno‐De‐Luca,
- Henry Houlden,
- Reza Maroofian
Affiliations
- Rauan Kaiyrzhanov
- Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology London WC1N 3BG UK
- Maha S. Zaki
- Human Genetics and Genome Research Division, Clinical Genetics Department National Research Centre Cairo Egypt
- Tracy Lau
- Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology London WC1N 3BG UK
- Sambuddha Sen
- Department of Chemistry and Biochemistry The Ohio State University 100 West 18th Avenue Columbus Ohio 43210 USA
- Reza Azizimalamiri
- Department of Paediatric Neurology, Golestan, Medical, Educational, and Research Center Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran
- Mina Zamani
- Department of Biology, Faculty of Science Shahid Chamran University of Ahvaz Ahvaz Iran
- Gözde Yeşil Sayin
- Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University Istanbul 34098 Turkey
- Taru Hilander
- Genetics Section, Molecular and Clinical Sciences St George's, University of London London UK
- Stephanie Efthymiou
- Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology London WC1N 3BG UK
- Viorica Chelban
- Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology London WC1N 3BG UK
- Ruth Brown
- Oxford Medical Genetics Laboratories The Churchill Hospital Oxford OX3 7LJ UK
- Kyle Thompson
- Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University Newcastle upon Tyne NE2 4HH UK
- Maria Irene Scarano
- Division of Genetics, Cooper Health System Children's Regional Hospital Sheridan Pavilion Camden New Jersy 08103 USA
- Jaya Ganesh
- Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USA
- Kairgali Koneev
- Department of Neurology and Neurosurgery Asfendiyarov Kazakh National Medical University Almaty 050000 Kazakhstan
- Ismail Musab Gülaçar
- Department of Medical Genetics, Istanbul Faculty of Medicine Istanbul University Istanbul 34098 Turkey
- Richard Person
- GeneDx Gaithersburg Maryland 20877 USA
- Dinara Sadykova
- Astana Medical University Nur‐Sultan Kazakhstan
- Yerdan Maidyrov
- Department of Neurology and Neurosurgery Asfendiyarov Kazakh National Medical University Almaty 050000 Kazakhstan
- Tahereh Seifi
- Department of Biology, Faculty of Science Shahid Chamran University of Ahvaz Ahvaz Iran
- Aizhan Zadagali
- L.N. Gumilyov Eurasian National University Nur‐Sultan Kazakhstan
- Geneviève Bernard
- Departments of Neurology and Neurosurgery, Pediatrics and Human Genetics McGill University Montreal Canada
- Katrina Allis
- GeneDx Gaithersburg Maryland 20877 USA
- Houda Zghal Elloumi
- GeneDx Gaithersburg Maryland 20877 USA
- Amanda Lindy
- GeneDx Gaithersburg Maryland 20877 USA
- Ehsan Taghiabadi
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences Tehran Iran
- Sumit Verma
- Department of Neurology Emory University School of Medicine Georgia Atlanta USA
- Rachel Logan
- Division of Neurosciences Children's Healthcare of Atlanta Atlanta Georgia USA
- Brian Kirmse
- Division of Genetics University of Mississippi Medical Center Jackson Mississippi USA
- Renkui Bai
- GeneDx Gaithersburg Maryland 20877 USA
- Shaimaa M. Khalaf
- Pediatrics Department Assiut University Assiut Egypt
- Mohamed S. Abdel‐Hamid
- Medical Molecular Genetics Department Human Genetics and Genome Research Institute, National Research Centre Cairo Egypt
- Alireza Sedaghat
- Health Research Institute, Diabetes Research Center Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran
- Gholamreza Shariati
- Department of Medical Genetics, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran
- Mahmoud Issa
- Human Genetics and Genome Research Division, Clinical Genetics Department National Research Centre Cairo Egypt
- Jawaher Zeighami
- Narges Medical Genetics and Prenatal Diagnosis Laboratory East Mihan Ave., Kianpars Ahvaz Iran
- Hasnaa M. Elbendary
- Human Genetics and Genome Research Division, Clinical Genetics Department National Research Centre Cairo Egypt
- Garry Brown
- Oxford Medical Genetics Laboratories The Churchill Hospital Oxford OX3 7LJ UK
- Robert W. Taylor
- Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University Newcastle upon Tyne NE2 4HH UK
- Hamid Galehdari
- Department of Biology, Faculty of Science Shahid Chamran University of Ahvaz Ahvaz Iran
- Joseph J. Gleeson
- Department of Neurosciences University of California, San Diego La Jolla California 92093 USA
- Christopher J. Carroll
- Genetics Section, Molecular and Clinical Sciences St George's, University of London London UK
- James A. Cowan
- Department of Chemistry and Biochemistry The Ohio State University 100 West 18th Avenue Columbus Ohio 43210 USA
- Andres Moreno‐De‐Luca
- Department of Radiology Autism & Developmental Medicine Institute, Genomic Medicine Institute Geisinger Danville Pennsylvania 17822 USA
- Henry Houlden
- Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology London WC1N 3BG UK
- Reza Maroofian
- Department of Neuromuscular Disorders UCL Queen Square Institute of Neurology London WC1N 3BG UK
- DOI
- https://doi.org/10.1002/acn3.51679
- Journal volume & issue
-
Vol. 9,
no. 12
pp. 2025 – 2035
Abstract
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.
