Possible mitochondrial disorder - nuclear genes
Gene: PDK3
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red. GMS reviewers believe that there is currently insufficient evidence that variants in this gene lead to primary mitochondrial disease (disease mechanism unclear; phenotype CMT; phenotype not consistent with known PDH deficiency disorders).Created: 1 Feb 2023, 1:12 p.m. | Last Modified: 1 Feb 2023, 5:02 p.m.
Panel Version: 2.5
At least two variants in three unrelated families reported (founder effect ruled out). Functional analyses conducted in patient fibroblasts, cell lines, and in vivo animal model (C. elegans) show that the recurrent variant (p.R158H) increased phosphorylation of the pyruvate dehydrogenase complex and thereby leads to significant reductions in ATP levels. Abnormal mitochondrial networks and mitochondrial trafficking were also reduced in affected axons.
Although energy metabolism defects and mitochondrial abnormalities are observed, the CMT phenotype presented by patients may not be relevant to this panel. For this reason, inclusion of PDK3 will be reviewed by the test evaluation group at the next GMS panel update.Created: 5 Jan 2022, 12:41 p.m. | Last Modified: 5 Jan 2022, 12:41 p.m.
Panel Version: 1.62
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905
Publications
Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.Created: 4 Feb 2019, 1:36 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
?Charcot-Marie-Tooth disease, X-linked dominant, 6, 300905
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Charcot-Marie-Tooth disease, X-linked dominant, 6, MIM#300905
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Tag Q1_22_rating was removed from gene: PDK3. Tag Q1_22_phenotype was removed from gene: PDK3. Tag Q1_22_expert_review was removed from gene: PDK3.
Tag Q1_22_expert_review tag was added to gene: PDK3.
Tag Q1_22_rating tag was added to gene: PDK3.
Publications for gene: PDK3 were set to
Tag Q1_22_phenotype tag was added to gene: PDK3.
gene: PDK3 was added gene: PDK3 was added to Possible mitochondrial disorder - nuclear genes. Sources: Expert Review Red,NHS GMS Mode of inheritance for gene: PDK3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: PDK3 were set to ?Charcot-Marie-Tooth disease, X-linked dominant, 6, 300905