Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation.

Adolescent Child Child, Preschool Cohort Studies Consanguinity Electron Transport Complex I / genetics Family Female Genetic Predisposition to Disease Humans Italy Leigh Disease / complications Male Mitochondrial Diseases / complications NADPH Dehydrogenase / genetics Phenotype Polymorphism, Single Nucleotide

Leigh syndrome NADH ubiquinone oxidoreductase NDUFA12 mitochondrial disease

Journal

Human mutation

ISSN: 1098-1004

Titre abrégé: Hum Mutat

Pays: United States

ID NLM: 9215429

Informations de publication

Date de publication:
06 2021

Historique:

revised: 27 01 2021

received: 08 09 2020

accepted: 06 03 2021

pubmed: 15 3 2021

medline: 29 1 2022

entrez: 14 3 2021

Statut: ppublish

Résumé

Isolated biochemical deficiency of mitochondrial complex I is the most frequent signature among mitochondrial diseases and is associated with a wide variety of clinical symptoms. Leigh syndrome represents the most frequent neuroradiological finding in patients with complex I defect and more than 80 monogenic causes have been involved in the disease. In this report, we describe seven patients from four unrelated families harboring novel NDUFA12 variants, with six of them presenting with Leigh syndrome. Molecular genetic characterization was performed using next-generation sequencing combined with the Sanger method. Biochemical and protein studies were achieved by enzymatic activities, blue native gel electrophoresis, and western blot analysis. All patients displayed novel homozygous mutations in the NDUFA12 gene, leading to the virtual absence of the corresponding protein. Surprisingly, despite the fact that in none of the analyzed patients, NDUFA12 protein was detected, they present a different onset and clinical course of the disease. Our report expands the array of genetic alterations in NDUFA12 and underlines phenotype variability associated with NDUFA12 defect.

Identifiants

DOI: 10.1002/humu.24195 PMID: 33715266

pubmed: 33715266

doi: 10.1002/humu.24195

doi:

Substances chimiques

NDUFA12 protein, human 0

NADPH Dehydrogenase EC 1.6.99.1

Electron Transport Complex I EC 7.1.1.2

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

699-710

Informations de copyright

Références

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