학술논문
Phenotypic continuum of NFU1‐related disorders
Document Type
article
Author
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
Source
Annals of Clinical and Translational Neurology, Vol 9, Iss 12, Pp 2025-2035 (2022)
Subject
Language
English
ISSN
2328-9503
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.