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Estimating the occurrence of primary ubiquinone deficiency by analysis of large-scale sequencing data.
- Source :
-
Scientific reports [Sci Rep] 2017 Dec 18; Vol. 7 (1), pp. 17744. Date of Electronic Publication: 2017 Dec 18. - Publication Year :
- 2017
-
Abstract
- Primary ubiquinone (UQ) deficiency is an important subset of mitochondrial disease that is caused by mutations in UQ biosynthesis genes. To guide therapeutic efforts we sought to estimate the number of individuals who are born with pathogenic variants likely to cause this disorder. We used the NCBI ClinVar database and literature reviews to identify pathogenic genetic variants that have been shown to cause primary UQ deficiency, and used the gnomAD database of full genome or exome sequences to estimate the frequency of both homozygous and compound heterozygotes within seven genetically-defined populations. We used known population sizes to estimate the number of afflicted individuals in these populations and in the mixed population of the USA. We then performed the same analysis on predicted pathogenic loss-of-function and missense variants that we identified in gnomAD. When including only known pathogenic variants, our analysis predicts 1,665 affected individuals worldwide and 192 in the USA. Adding predicted pathogenic variants, our estimate grows to 123,789 worldwide and 1,462 in the USA. This analysis predicts that there are many undiagnosed cases of primary UQ deficiency, and that a large proportion of these will be in developing regions of the world.
- Subjects :
- Databases, Nucleic Acid
Exome
Gene Frequency
High-Throughput Nucleotide Sequencing methods
Humans
Mutation genetics
Phenotype
Ubiquinone genetics
Ubiquinone physiology
Exome Sequencing
Ataxia epidemiology
Ataxia genetics
Mitochondrial Diseases epidemiology
Mitochondrial Diseases genetics
Muscle Weakness epidemiology
Muscle Weakness genetics
Ubiquinone deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29255295
- Full Text :
- https://doi.org/10.1038/s41598-017-17564-y