Correia 2021 Hum Mutat
|Correia SP, Moedas MF, Naess K, Bruhn H, Maffezzini C, Calvo-Garrido J, Lesko N, Wibom R, Schober FA, Jemt A, Stranneheim H, Freyer C, Wedell A, Wredenberg A (2021) Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7. Hum Mutat [Epub ahead of print].|
Correia Sandrina P, Moedas Marco F, Naess Karin, Bruhn Helene, Maffezzini Camilla, Calvo-Garrido Javier, Lesko Nicole, Wibom Rolf, Schober Florian A, Jemt Anders, Stranneheim Henrik, Freyer Christoph, Wedell Anna, Wredenberg Anna (2021) Hum Mutat
Abstract: 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.
• Keywords: NDUFB7, Cryptic splice site mutation, Intrauterine clinical manifestations, Isolated complex I deficiency, Mitochondrial disease • Bioblast editor: Plangger M
Labels: MiParea: Respiration, nDNA;cell genetics
Organism: Human Tissue;cell: Fibroblast Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS Pathway: N, S, NS HRR: Oxygraph-2k