A novel complex neurological phenotype due to a homozygous mutation in FDX2

Brain : a Journal of Neurology
Juliana Gurgel-GiannettiFernando Kok

Abstract

Defects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leuk...Continue Reading

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Citations

Apr 6, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Samya BanerjeePeter J Sadler
Jun 20, 2020·Scientific Reports·Hee-Ju KangJae-Min Kim
Jun 6, 2020·Cell Death & Disease·Jesse D SloneTaosheng Huang
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Feb 1, 2022·IUBMB Life·Nunziata Maio, Tracey A Rouault

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