Hereditary neuropathy or pain disorder
Gene: PDK3
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 10:16 a.m. | Last Modified: 7 Jan 2024, 7:44 p.m.
Panel Version: 3.74
Comment on list classification: At least two variants in three unrelated families reported (founder effect ruled out), as well as functional analyses conducted in patient fibroblasts, cell lines, and animal model. This supports a rating upgrade on this panel from Amber to Green at the next GMS panel update (tagged).Created: 5 Jan 2022, 12:15 p.m. | Last Modified: 5 Jan 2022, 12:15 p.m.
Panel Version: 1.79
Narayanan et al., 2021 (PMID: 34387338) developed a C. elegans model of CMTX6 by knocking-in the p.R158H variant in the orthologous PDK3 gene and by expressing the mutant form of human PDK3 specifically in the GABAergic motor neurons of C. elegans. Mutants exhibited axon-associated synaptic transmission deficits, locomotion defects, signs of progressive neurodegeneration and also displayed ATP deficits that recapitulate phenotypes observed in patient fibroblasts and iPSC-derived motor neurons.Created: 5 Jan 2022, noon | Last Modified: 5 Jan 2022, noon
Panel Version: 1.78
Phenotypes
Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905
Publications
One Australian, one Korean family identified with same variant. Additional case reported in a cohort of neuropathy patients, different variant. Some functional data.Created: 1 Apr 2020, 9:30 a.m. | Last Modified: 1 Apr 2020, 9:30 a.m.
Panel Version: 1.4
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Charcot-Marie-Tooth disease, X-linked dominant, 6 MIM#300905; HMSN
Publications
Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 29 Apr 2019, 12:53 p.m.
2 families and some functional work. PMID: 23297365 (Kennerson et al, 2013) Australian family appears to segregateand some functional work; PMID: 26801680 (Kennerson et al, 2016) Korean familyCreated: 29 Apr 2019, 12:30 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
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Await further evidence before promote to green listCreated: 8 Jul 2016, 4:01 a.m.
Comment on publications: Two families have now been reported with the p.R158H mutation, though this is still not enough evidence to be rated green, with only one known Charcot-Marie-Tooth disease-causing variant in this gene reported to date.Created: 5 May 2016, 9:22 a.m.
Comment on mode of inheritance: Seems to be X-linked dominant (monoallelic mutations in females could cause the disorder).Created: 5 May 2016, 9:19 a.m.
Now 2 families, likely pathogenicCreated: 16 May 2019, 4:21 p.m.
Single familyCreated: 9 Dec 2015, 8:50 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Single familyCreated: 8 Dec 2015, 3:06 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Tag Q1_22_rating was removed from gene: PDK3.
Source Expert Review Green was added to PDK3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: PDK3 were set to 26801680; 23297365
Tag Q1_22_rating tag was added to gene: PDK3.
Gene: pdk3 has been classified as Amber List (Moderate Evidence).
Gene: pdk3 has been classified as Amber List (Moderate Evidence).
gene: PDK3 was added gene: PDK3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert Review Red,South West GLH,Radboud University Medical Center, Nijmegen 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) Publications for gene: PDK3 were set to 26801680; 23297365 Phenotypes for gene: PDK3 were set to ?Charcot Marie Tooth disease, X linked dominant, 6, 300905