COQ7 defect causes prenatal onset of mitochondrial CoQ 10 deficiency with cardiomyopathy and gastrointestinal obstruction.
Ilaria PettenuzzoSara CarliAna Sánchez-CuestaFederica IsidoriFrancesca MontanariMina GrippaGiulia LanzoniIrene AmbrosettiVeronica Di PisaDuccio Maria CordelliMaria Cristina MondardiniTommaso PippucciLuca RagniGiovanna CenacchiRoberta CostaMario LimaMaria Antonietta CapristoConcetta Valentina TropeanoLeonardo CaporaliValerio CarelliElena BrunelliMonica MaffeiHodman Ahmed SheikhmayeAnna FettaGloria Brea CalvoCaterina GaronePublished in: European journal of human genetics : EJHG (2024)
COQ7 pathogenetic variants cause primary CoQ 10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ 10 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 CoQ 10 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 CoQ 10 (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 CoQ 10 deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.
Keyphrases
- aortic valve
- copy number
- hypertrophic cardiomyopathy
- left ventricular
- high dose
- early onset
- heart failure
- pregnant women
- genome wide
- newly diagnosed
- oxidative stress
- ejection fraction
- skeletal muscle
- dna methylation
- single cell
- pseudomonas aeruginosa
- escherichia coli
- low dose
- preterm infants
- gestational age
- staphylococcus aureus
- pulmonary arterial hypertension
- mitral valve
- drug induced
- chronic kidney disease
- quality improvement
- acute coronary syndrome
- molecular docking
- intellectual disability
- genome wide identification
- patient reported
- high grade
- percutaneous coronary intervention
- biofilm formation
- cardiac resynchronization therapy