Congenital myopathy

Gene: MT-TK

Red List (low evidence)

After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to red. GLH review concluded that mitochondrial myopathies are not good fit for this panel. R300 Possible mitochondrial disorder - whole mitochondrial genome sequencing would be the more appropriate test.

Created: 11 Dec 2025, 5:32 p.m. | Last Modified: 11 Dec 2025, 5:32 p.m.

Panel Version: 6.43

Comment on list classification: As reviewed by Katherine Schon, myopathy is one of the clinical presentations of MERFF syndrome caused by m.8344A>G variant in MT-TK gene. However, it should be noted that the onset of myopathic features is not during infancy or first few years of life in the reported patients. Hence, expert review is sought from the Genomic Medicine Service on upgrading this gene to green rating on this panel.

Created: 27 Jun 2025, 9:20 a.m. | Last Modified: 27 Jun 2025, 9:20 a.m.

Panel Version: 6.16

As per MitoPhen database (https://www.mitophen.org) there are >30 patients reported with m.8344A>G variant in MT-TK gene and with myopathy as one of the presentations. However, it appears that myopathic features had a later onset even in patients that had onset of other phenotypes of myoclonus epilepsy and ragged-red fibers (MERRF) in infancy/ early childhood.

PMID:1463006 - Three different families reported with MERRF and m.8344A>G variant. The probands had the first onset of symptoms at 0.5, 5 and 9 years respectively. However, the reports of muscle weakness were reported later (starting from the ages of 10, 21 and 17 years in there three probands).

PMID:8228033 - Two siblings were reported with MERRF and m.8344A>G variant. Although both siblings complained of fatigue since early childhood, muscle weakness was only reported much later.

Created: 27 Jun 2025, 9:12 a.m. | Last Modified: 27 Jun 2025, 9:12 a.m.

Panel Version: 6.13

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MERRF syndrome, MONDO:0010790; inborn mitochondrial myopathy, MONDO:0009637

Publications

• 1463006
• 8228033

Green List (high evidence)

Myopathy is a recognised part of the phenotype in MERRF (m.8344A>G variant).

Created: 24 Jun 2025, 10:53 a.m. | Last Modified: 24 Jun 2025, 10:53 a.m.

Panel Version: 6.10

Mode of inheritance
MITOCHONDRIAL

Mode of pathogenicity
Other