Toggle Main Menu Toggle Search

Open Access padlockePrints

Phenotypic continuum of NFU1-related disorders

Lookup NU author(s): Dr Kyle Thompson, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.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.

Publication metadata

Author(s): Kaiyrzhanov R, Zaki MS, Lau T, Sen S, Azizimalamiri R, Zamani M, Sayin GY, Hilander T, Efthymiou S, Chelban V, Brown R, Thompson K, Scarano MI, Ganesh J, Koneev K, Gulacar IM, Person R, Sadykova D, Maidyrov Y, Seifi T, Zadagali A, Bernard G, Allis K, Elloumi HZ, Lindy A, Taghiabadi E, Verma S, Logan R, Kirmse B, Bai R, Khalaf SM, Abdel-Hamid MS, Sedaghat A, Shariati G, Issa M, Zeighami J, Elbendary HM, Brown G, Taylor RW, Galehdari H, Gleeson JJ, Carroll CJ, Cowan JA, Moreno-De-Luca A, Houlden H, Maroofian R

Publication type: Article

Publication status: Published

Journal: Annals of Clinical and Translational Neurology

Year: 2022

Volume: 9

Issue: 12

Pages: 2025-2035

Print publication date: 10/12/2022

Online publication date: 18/10/2022

Acceptance date: 29/09/2022

Date deposited: 02/11/2022

ISSN (electronic): 2328-9503

Publisher: John Wiley and Sons Inc


DOI: 10.1002/acn3.51679


Altmetrics provided by Altmetric


Funder referenceFunder name
203105/Z/16/ZWellcome Trust
Medical Research Council. Grant Numbers: G0802760, G1001253, MR/J004758/1, MR/W019027/1
MR/S005021/1Medical Research Council (MRC)
Wellcome Centre for Mitochondrial Research. Grant Number: 203105/Z/16/Z
The Medical Research Council International Centre for Genomic Medicine in Neuromuscular Disease. Grant Number: MR/S005021/1
Wellcome Trust. Grant Number: 104033