Coenzyme Q10 Deficiency, Primary, 2

A number sign (#) is used with this entry because of evidence that primary coenzyme Q10 deficiency-2 (COQ10D2) is caused by homozygous mutation in the PDSS1 gene (607429) on chromosome 10p12. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426).

Clinical Features

Mollet et al. (2007) reported 2 sibs, born of consanguineous Moroccan parents, in which CoQ10 deficiency was manifest as a multisystem disorder with early-onset deafness, optic atrophy, mild mental retardation, peripheral neuropathy, obesity, livedo reticularis, and cardiac valvulopathy. The patients were 22 and 14 years old at the time of the report. Enzymologic analysis showed low quinone-dependent oxidative phosphorylation activity in affected members, and CoQ10 deficiency was confirmed by restoration of oxidative phosphorylation activity after quinone addition. Patient fibroblasts showed low CoQ10 levels.

Inheritance

The transmission pattern of CoQ10 deficiency in the family reported by Mollet et al. (2007) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 2 Moroccan sibs with CoQ10 deficiency, Mollet et al. (2007) identified a homozygous mutation in the PDSS1 gene (D308E; 607429.0001). The mutation was found by homozygosity mapping followed by candidate gene analysis. Transformation of yeast lacking Coq1 with yeast Coq1 containing a mutation corresponding to human D308E resulted in defective growth on respiratory medium.