(HealthDay)—Functionally impaired variants in the COQ2 gene, which encodes the enzyme parahydroxybenzoate-polyprenyl transferase, have been identified in multiplex families with multiple-system atrophy and in patients with sporadic disease, according to a study published online June 12 in the New England Journal of Medicine.
Jun Mitsui, M.D., Ph.D., from the University of Tokyo, and colleagues performed whole-genome sequencing of a sample obtained from a member of a multiplex family with multiple-system atrophy. Mutational analysis was also performed on samples from members of five other families, and from three patient series (Japanese, European, and North American). Enzyme activity of parahydroxybenzoate-polyprenyl transferase was measured.
In two multiplex families, the researchers identified a homozygous mutation (M78V-V343A/M78V-V343A) and compound heterozygous mutations (R337X/V343A) in COQ2. A common variant (V343A) and multiple rare variants were also identified in COQ2, all of which were functionally impaired and were linked with sporadic multiple-system atrophy. The variant V343A was only seen in the Japanese series.
"Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease, providing evidence of a role [for] impaired COQ2 activities in the pathogenesis of this disease," the authors write.