Congenital muscular dystrophy and congenital myopathy

Gene: SLC25A4

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
mitochondrial myopathy

Publications

• 25732997
• 27693233

Green List (high evidence)

Comment when marking as ready: In light of the red review by an expert a further opinion was sought. Discussed with Arianna Tucci, genomics England curator who has reviewed the evidence. Although myopathy is not the only presenting feature, it is a key feature and therefore felt to be appropriate for inclusion to reflect the broader aspects of the phenotype. Keep as green

Created: 7 Mar 2017, 2:37 p.m.

Comment when marking as ready: Sufficient evidence for match with the phenotype at least for two recurrent missense mutations; c.239G>A (p.Arg80His) and c.703C>G (p.Arg235Gly). However, important to note that other monoallelic and biallelic mutations in this gene do cause disease, but not necessarily this phenotype (Progressive external ophthalmolplegia and adult onset of exercise intolerance with raised lactate)

Created: 3 Feb 2017, 2:43 p.m.

Comment on list classification: 6 unrelated families described in above PMID in relation to de novo dominant mitochondrial depletion syndrome. Presenting features were profound weakness and respiratory insufficiency at birth. Many would also have lactic acidosis / encephalopathy / cardiomyopathy and therefore not a classic presentation of pure congenital myopathy, however given the early onset of profound weakness it could be appropriate to include.

Created: 3 Feb 2017, 2:41 p.m.

Comment on mode of inheritance: De novo recurrent mutations associated with congenital onset of weakness / respiratory insufficiency (in association with lactic acidosis and encephalopathy in some) c.239G>A (p.Arg80His) and c.703C>G (p.Arg235Gly). Biallelic case reported with adult onset and also monoallelic mutations reported in adult onset PEO

Created: 3 Feb 2017, 2:40 p.m.

6 unrelated families described in above PMID in relation to de novo dominant mitochondrial depletion syndrome. Presenting features were profound weakness and respiratory insufficiency at birth. Many would also have lactic acidosis / encephalopathy / cardiomyopathy and therefore not a classic presentation of pure congenital myopathy, however given the early onset of profound weakness it could be appropriate to include.

Created: 31 Jan 2017, 12:48 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD 617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR 615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 609283

Publications

• PMID 27693233

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mitochondrial myopathy

Publications

• PMID:25732997