Discussion
This work confirms the importance of COQ8A gene mutations as a frequent genetic cause of cerebellar ataxia and CoQ10 deficiency and suggests SPG7 mutations as a novel cause of secondary CoQ10 deficiency.
Methods
WES was performed on genomic DNA extracted from 16 patients. Sequencing data were filtered using a virtual panel of genes associated with CoQ10 deficiency and/or cerebellar ataxia. CoQ10 levels were measured by high-performance liquid chromatography in 14 patient-derived fibroblasts.
Results
A definite genetic etiology was identified in 8 samples of 16 (diagnostic yield = 50%). The identified genetic causes were pathogenic variants of the genes COQ8A (ADCK3) (n = 3 samples), ATP1A3 (n = 2), PLA2G6 (n = 1), SPG7 (n = 1), and MFSD8 (n = 1). Five novel mutations were found (COQ8A n = 3, PLA2G6 n = 1, and MFSD8 n = 1). CoQ10 levels were significantly decreased in 3/14 fibroblast samples (21.4%), 1 carrying compound heterozygous COQ8A pathogenic variants, 1 harboring a homozygous pathogenic SPG7 variant, and 1 with an unknown molecular defect.