z-logo
Premium
Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7
Author(s) -
Correia Sandrina P.,
Moedas Marco F.,
Naess Karin,
Bruhn Helene,
Maffezzini Camilla,
CalvoGarrido Javier,
Lesko Nicole,
Wibom Rolf,
Schober Florian A.,
Jemt Anders,
Stranneheim Henrik,
Freyer Christoph,
Wedell Anna,
Wredenberg Anna
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24173
Subject(s) - lactic acidosis , biology , mutation , intron , exon , complementation , genetics , hypertrophic cardiomyopathy , rna splicing , compound heterozygosity , gene , microbiology and biotechnology , rna , endocrinology , phenotype , biochemistry
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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here