Dataset Information

COQ7 defect causes prenatal onset of mitochondrial CoQ₁₀ deficiency with cardiomyopathy and gastrointestinal obstruction.

ABSTRACT: COQ7 pathogenetic variants cause primary CoQ₁₀ deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ₁₀ supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ₁₀ levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ₁₀ (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ₁₀ deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.

SUBMITTER: Pettenuzzo I

PROVIDER: S-EPMC11291740 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction.

Pettenuzzo Ilaria I Carli Sara S Sánchez-Cuesta Ana A Isidori Federica F Montanari Francesca F Grippa Mina M Lanzoni Giulia G Ambrosetti Irene I Di Pisa Veronica V Cordelli Duccio Maria DM Mondardini Maria Cristina MC Pippucci Tommaso T Ragni Luca L Cenacchi Giovanna G Costa Roberta R Lima Mario M Capristo Maria Antonietta MA Tropeano Concetta Valentina CV Caporali Leonardo L Carelli Valerio V Brunelli Elena E Maffei Monica M Ahmed Sheikhmaye Hodman H Fetta Anna A Brea-Calvo Gloria G Garone Caterina C

European journal of human genetics : EJHG 20240503 8

COQ7 pathogenetic variants cause primary CoQ10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ10 supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. T ...[more]

PMID: 38702428

Similar Datasets

Project description:BackgroundOxidative stress is highly prevalent in patients with end-stage renal disease and is linked to excess cardiovascular risk. Identifying therapies that reduce oxidative stress has the potential to improve cardiovascular outcomes in patients undergoing maintenance dialysis.Study designPlacebo-controlled, 3-arm, double-blind, randomized, clinical trial.Setting & participants65 patients undergoing thrice-weekly maintenance hemodialysis.InterventionPatients were randomly assigned in a 1:1:1 ratio to receive once-daily coenzyme Q10 (CoQ10; 600 or 1,200mg) or matching placebo for 4 months.OutcomesThe primary outcome was plasma oxidative stress, defined as plasma concentration of F2-isoprotanes. Secondary outcomes included levels of plasma isofurans, levels of cardiac biomarkers, predialysis blood pressure, and safety/tolerability.MeasurementsF2-isoprostanes and isofurans were measured as plasma markers of oxidative stress, and N-terminal pro-brain natriuretic peptide and troponin T were measured as cardiac biomarkers at baseline and 1, 2, and 4 months.ResultsOf 80 randomly assigned patients, 15 were excluded due to not completing at least 1 postbaseline study visit and 65 were included in the primary intention-to-treat analysis. No treatment-related major adverse events occurred. Daily treatment with 1,200mg, but not 600mg, of CoQ10 significantly reduced plasma F2-isoprostanes concentrations at 4 months compared to placebo (adjusted mean changes of -10.7 [95% CI, -7.1 to -14.3] pg/mL [P<0.001] and -8.3 [95% CI, -5.5 to -11.0] pg/mL [P=0.1], respectively). There were no significant effects of CoQ10 treatment on levels of plasma isofurans, cardiac biomarkers, or predialysis blood pressures.LimitationsStudy not powered to detect small treatment effects; difference in baseline characteristics among randomized groups.ConclusionsIn patients undergoing maintenance hemodialysis, daily supplementation with 1,200mg of CoQ10 is safe and results in a reduction in plasma concentrations of F2-isoprostanes, a marker of oxidative stress. Future studies are needed to determine whether CoQ10 supplementation improves clinical outcomes for patients undergoing maintenance hemodialysis.

Dataset Information

COQ7 defect causes prenatal onset of mitochondrial CoQ₁₀ deficiency with cardiomyopathy and gastrointestinal obstruction.

Publications

COQ7 defect causes prenatal onset of mitochondrial CoQ<sub>10</sub> deficiency with cardiomyopathy and gastrointestinal obstruction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets