Mitochondrial disease

Gene: PDK3

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, 12:05 p.m. | Last Modified: 5 Jan 2022, 12:05 p.m.

Panel Version: 0.10519

Phenotypes
Charcot-Marie-Tooth disease, X-linked dominant, 6, OMIM:300905

Publications

• 34387338

Green List (high evidence)

Two unrelated families with the same variant and a single CMT case with another variant, and functional analyses conducted in patient fibroblasts and cell lines.
Sources: Expert list

Created: 23 Mar 2020, 3:27 a.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 MIM#300905; HMSN

Publications

• 23297365
• 26801680
• 27388934
• 28902413

Green List (high evidence)

Three families reported with a CMT phenotype, two families with a recurrent p.R158H (not a founder effect).

Created: 18 Mar 2020, 1:04 a.m. | Last Modified: 18 Mar 2020, 1:04 a.m.

Panel Version: 0.156

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

• 23297365
• 28902413
• 26801680