Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0036572 (
seizures
)
80,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Primary coenzyme Q10 (CoQ
10
; MIM# 607426) deficiencies are an emerging group of inherited mitochondrial disorders with heterogonous clinical phenotypes. Over a dozen genes are involved in the biosynthesis of CoQ
10
, and mutations in several of these are associated with human disease. However, mutations in
COQ5
(MIM# 616359), catalyzing the only C-methylation in the CoQ
10
synthetic pathway, have not been implicated in human disease. Here, we report three female siblings of Iraqi-Jewish descent, who had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic-clonic
seizures
, and cognitive disability. Whole-exome and subsequent whole-genome sequencing identified biallelic duplications in the
COQ5
gene, leading to reduced levels of CoQ
10
in peripheral white blood cells of all affected individuals and reduced CoQ
10
levels in the only muscle tissue available from one affected proband. CoQ
10
supplementation led to clinical improvement and increased the concentrations of CoQ
10
in blood. This is the first report of primary CoQ
10
deficiency caused by loss of function of
COQ5
, with delineation of the clinical, laboratory, histological, and molecular features, and insights regarding targeted treatment with CoQ
10
supplementation.
...
PMID:A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency. 2904 65
