Hereditary neuropathy or pain disorder

Gene: MT-ND6

Red List (low evidence)

As reviewed by Dmitrijs Rots, MT-ND6 is associated with Leber hereditary optic neuropathy (LHON) and GeneReviews (PMID:20301353) states that it includes neurological abnormalities including peripheral neuropathy. Review of cited publications from GeneReviews (PMIDs:17724295 & 27111573) showed that patients with MT-ND6 variants presented with dystonia and other movement disorders. I cannot find any association to peripheral neuropathy in these publications.

However, PMID:38975939 reported the identification of a homoplasmic variant in MT-ND6 gene (p.Met64Val) in a patient with chronic progressive ataxic neuropathy.

This gene has not been associated with any relevant phenotypes in OMIM or in Gen2Phenotype. In addition, this gene is not associated with any of the hereditary neuropathy panels in PanelApp Australia.

Hence, this gene should only be rated red with the available evidence.

Created: 14 Nov 2024, 2:10 p.m. | Last Modified: 14 Nov 2024, 2:10 p.m.

Panel Version: 6.131

Mode of inheritance
MITOCHONDRIAL

Publications

• 17724295
• 20301353
• 27111573
• 38975939

Green List (high evidence)

Gene is associated with LHON, but GeneReviews states: "Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific myopathy, and movement disorders have been reported to be more common in individuals with LHON than in the general population. ".
Identified in our lab in a young patient with peripheral neuropathy phenotype only.
Sources: Literature

Created: 20 Oct 2023, 6:14 p.m.

Mode of inheritance
MITOCHONDRIAL

Phenotypes
LHON; peripheral neuropathy

Publications

• PMID: 20301353

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments