Phenotypic continuum of NFU1-related disorders.
Rauan KaiyrzhanovMaha S ZakiTracy LauSambuddha SenReza AzizimalamiriMina ZamaniGözde Yeşil SayinTaru HilanderStephanie EfthymiouViorica ChelbanRuth BrownKyle ThompsonMaria Irene ScaranoJaya GaneshKairgali KoneevIsmail Musab GülaçarRichard PersonDinara SadykovaYerdan MaidyrovTahereh SeifiAizhan ZadagaliGeneviève BernardKatrina AllisHouda Zghal ElloumiAmanda LindyEhsan TaghiabadiSumit VermaRachel LoganBrian KirmseRenkui BaiShaimaa M KhalafMohamed S Abdel-HamidAlireza SedaghatGholamreza ShariatiMahmoud Y IssaJawaher ZeighamiHasnaa M ElbendaryGarry BrownRobert W TaylorHamid GalehdariJoseph J GleesonChristopher J CarrollJames A CowanAndrés Moreno De LucaHenry HouldenReza MaroofianPublished in: Annals of clinical and translational neurology (2022)
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.
Keyphrases
- early onset
- late onset
- white matter
- heat shock protein
- copy number
- heat shock
- heat stress
- oxidative stress
- high resolution
- multiple sclerosis
- intellectual disability
- case report
- autism spectrum disorder
- urinary tract infection
- botulinum toxin
- dna methylation
- free survival
- blood brain barrier
- drug induced
- cerebral ischemia