2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Phenotypic and molecular characterization of a cohort of patients with primary CoQ10 deficiency caused by pathogenic variants in <em>COQ7</em>

Pdf Summary

Primary CoQ10 deficiency is a genetic disorder caused by variants in genes involved in the production of CoQ10, a molecule important for cellular energy production. These variants can lead to a range of symptoms, from severe progressive encephalomyopathy to isolated organ involvement. One gene associated with this deficiency is COQ7, which encodes a protein involved in CoQ10 synthesis.<br /><br />Researchers studied five new patients with variants in the COQ7 gene. Clinical evaluations revealed two main clinical phenotypes associated with COQ7-related disorder: a neonatal-onset multisystemic disease and a late-onset progressive neuropathy. Patients with neonatal-onset disease often had prenatal complications such as oligohydramnios and intrauterine growth restriction, along with symptoms such as hypotonia, spasticity, developmental delay, and hearing impairment. Some also had lung, cardiac, and renal involvement.<br /><br />In contrast, patients with late-onset disease had symptoms such as lower extremity weakness, abnormal gait, and hearing impairment, but did not have renal or respiratory involvement. The age of onset ranged from 14 months to 12 years, and there were variations in the disease course.<br /><br />To investigate the functional effect of the COQ7 variants, the researchers used Baker's yeast as a disease model. They found that certain variants partially rescued the growth defects in yeast, while others showed a complete inability to grow. This suggests that some variants are hypomorphic (partially functional) alleles, while others are amorphic (non-functional) alleles.<br /><br />The researchers also found a correlation between the severity of clinical symptoms and residual activity of the COQ7 protein. Higher residual activity was associated with milder clinical severity.<br /><br />In conclusion, this study identified two disease presentations associated with COQ7 variants and validated the use of yeast as a model system for studying these variants. Understanding the genotype-phenotype correlation can help in diagnosing and managing patients with primary CoQ10 deficiency.

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Presenting Author - Parith Wongkittichote, MD. PhD; Co-Author - Laura Duque Lasio, MD; Co-Author - Martina Magistrati, PhD; Co-Author - Sheel Pathak, MD; Co-Author - Brooke Sample, MS; Co-Author - Daniel R. Carvalho, MD; Co-Author - Adrianna Banzzatto Ortega, MD; Co-Author - Claudio M. de Gusmao, MD; Co-Author - Matheus Castro, MD; Co-Author - Tomi L. Toler, MS; Co-Author - Emanuele Bellacchio, PhD; Co-Author - Cristina Dallabona, PhD; Co-Author - Marwan Shinawi;

Meta Tag

Biochemical genetics

Brain/Nervous System

Metabolic Disorder

Mitochondria

Model Organisms

Co-Author Laura Duque Lasio, MD

Co-Author Martina Magistrati, PhD

Co-Author Sheel Pathak, MD

Co-Author Brooke Sample, MS

Co-Author Daniel R. Carvalho, MD

Co-Author Adrianna Banzzatto Ortega, MD

Co-Author Claudio M. de Gusmao, MD

Co-Author Matheus Castro, MD

Co-Author Tomi L. Toler, MS

Co-Author Emanuele Bellacchio, PhD

Co-Author Cristina Dallabona, PhD

Co-Author Marwan Shinawi

Presenting Author Parith Wongkittichote, MD. PhD

Keywords

CoQ10 deficiency

genetic disorder

variants

genes

cellular energy production

COQ7 gene

neonatal-onset multisystemic disease

late-onset progressive neuropathy

residual activity

genotype-phenotype correlation