Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.

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

Hum. Mutat. 42 (4) 378-384 [2021-04-00; online 2021-02-04]

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.

Clinical Genomics Stockholm [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

PubMed 33502047

DOI 10.1002/humu.24173

Crossref 10.1002/humu.24173