Mitochondrial disease

Gene: TWNK

Green List (high evidence)

PMID: 32234020: Fig 1 shows variant distribution for all condition: - Missense within the linker region have only been reported for PEOA (AD). No other patterns for AD vs AR missense. - Missense in N-terminal motifs generally cause PEOA - PTCs reported for AR conditions - Same variant has been reported for both AR Perrault and mito depletion conditions (p.N399S). PMID: 18593709: Missense transfected into Schneider cells could form hexamers, had no effect on protein expression, had both loss and gain of mtDNA copy numbers and loss of ATPase activity when overexpressed with endogenous protein. No evidence of GOF mechanism found.

Created: 29 Jul 2020, 12:08 a.m. | Last Modified: 29 Jul 2020, 12:08 a.m.

Panel Version: 0.449

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286

Publications

• 32234020
• 18593709

Green List (high evidence)

PMID: 32234020: Fig 1 shows variant distribution for all condition:
- Missense within the linker region have only been reported for PEOA (AD). No other patterns for AD vs AR missense.
- Missense in N-terminal motifs generally cause PEOA
- PTCs reported for AR conditions
- Same variant has been reported for both AR Perrault and mito depletion conditions (p.N399S).

PMID: 18593709: Missense transfected into Schneider cells could form hexamers, had no effect on protein expression, had both loss and gain of mtDNA copy numbers and loss of ATPase activity when overexpressed with endogenous protein
No evidence of GOF mechanism found

Created: 28 Jul 2020, 11:51 p.m. | Last Modified: 28 Jul 2020, 11:51 p.m.

Panel Version: 0.3551

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286

Publications

• PMID: 32234020
• 18593709

Mode of pathogenicity
Other