Novel NDUFA13 Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report.
Adrián González-QuintanaInés García-ConsuegraAmaya Belanger-QuintanaPablo Serrano-LorenzoAlejandro LuciaAlberto BlázquezJorge DocampoCristina UgaldeMaría MoránJoaquín ArenasMiguel Angel MartinPublished in: Genes (2020)
Leigh syndrome (LS) usually presents as an early onset mitochondrial encephalopathy characterized by bilateral symmetric lesions in the basal ganglia and cerebral stem. More than 75 genes have been associated with this condition, including genes involved in the biogenesis of mitochondrial complex I (CI). In this study, we used a next-generation sequencing (NGS) panel to identify two novel biallelic variants in the NADH:ubiquinone oxidoreductase subunit A13 (NDUFA13) gene in a patient with isolated CI deficiency in skeletal muscle. Our patient, who represents the second family report with mutations in the CI NDUFA13 subunit, presented with LS lesions in brain magnetic resonance imaging, mild hypertrophic cardiomyopathy, and progressive spastic tetraparesis. This phenotype manifestation is different from that previously described in the first NDUFA13 family, which was predominantly characterized by neurosensorial symptoms. Both in silico pathogenicity predictions and oxidative phosphorylation (OXPHOS) functional findings in patient's skin fibroblasts (delayed cell growth, isolated CI enzyme defect, decreased basal and maximal oxygen consumption and as well as ATP production, together with markedly diminished levels of the NDUFA13 protein, CI, and respirasomes) suggest that these novel variants in the NDUFA13 gene are the underlying cause of the CI defect, expanding the genetic heterogeneity of LS.
Keyphrases
- copy number
- early onset
- case report
- genome wide
- hypertrophic cardiomyopathy
- magnetic resonance imaging
- skeletal muscle
- late onset
- oxidative stress
- genome wide identification
- multiple sclerosis
- dna methylation
- computed tomography
- left ventricular
- metabolic syndrome
- heart rate
- amino acid
- insulin resistance
- adipose tissue
- magnetic resonance
- contrast enhanced
- gene expression
- escherichia coli
- cystic fibrosis
- soft tissue
- blood brain barrier
- autism spectrum disorder
- transcription factor
- atrial fibrillation
- biofilm formation
- subarachnoid hemorrhage
- small molecule
- pseudomonas aeruginosa
- molecular dynamics simulations
- candida albicans