Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.
NDUFB7
cryptic splice site mutation
intrauterine clinical manifestations
isolated complex I deficiency
mitochondrial disease
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
18
12
2020
received:
21
08
2020
accepted:
24
01
2021
pubmed:
28
1
2021
medline:
1
4
2022
entrez:
27
1
2021
Statut:
ppublish
Résumé
Mutations in structural subunits and assembly factors of complex I of the oxidative phosphorylation system constitute the most common cause of mitochondrial respiratory chain defects. Such mutations can present a wide range of clinical manifestations, varying from mild deficiencies to severe, lethal disorders. We describe a patient presenting intrauterine growth restriction and anemia, which displayed postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with fatal outcome. Whole genome sequencing revealed an intronic biallelic mutation in the NDUFB7 gene (c.113-10C>G) and splicing pattern alterations in NDUFB7 messenger RNA were confirmed by RNA Sequencing. The detected variant resulted in a significant reduction of the NDUFB7 protein and reduced complex I activity. Complementation studies with expression of wild-type NDUFB7 in patient fibroblasts normalized complex I function. Here we report a case with a primary complex I defect due to a homozygous mutation in an intron region of the NDUFB7 gene.
Substances chimiques
NDUFB7 protein, human
0
NADH, NADPH Oxidoreductases
EC 1.6.-
Electron Transport Complex I
EC 7.1.1.2
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
378-384Informations de copyright
© 2021 The Authors. Human Mutation published by Wiley Periodicals LLC.
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