Prepair 1000+

Gene: TK2

Green List (high evidence)

TK2-related mitochondrial DNA (mtDNA) maintenance defect is a phenotypic continuum that ranges from severe to mild (GeneReviews PMID: 23230576).

Three main subtypes of presentation have been described (PMID: 23230576):
- Infantile-onset myopathy with neurologic involvement and rapid progression to early death. Affected individuals experience progressive muscle weakness leading to respiratory failure. Some individuals develop dysarthria, dysphagia, and/or hearing loss. Cognitive function is typically spared.
- Juvenile/childhood onset with generalized proximal weakness and survival to at least 13 years.
- Late-/adult-onset myopathy with facial and limb weakness and mtDNA deletions. Some affected individuals develop respiratory insufficiency, chronic progressive external ophthalmoplegia, dysphagia, and dysarthria.

It is possible that the range of phenotypes observed may be explained by the variability in the amount of residual activity of mutated enzymes (GeneReviews PMID: 23230576).

Therefore, a case-by-case analysis for each variant is warranted to determine reportability for Prepair+.

NB: the other phenotype listed in OMIM, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 MIM#617069, has been reported in one family and onset was in mid-forties. According to the current evidence, it is not relevant for Prepair+.

Created: 5 Feb 2025, 2:52 a.m. | Last Modified: 5 Feb 2025, 2:52 a.m.

Panel Version: 1.1456

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 2 (myopathic type) MIM#609560

Publications

• 23230576