Congenital myopathy
Gene: SLC25A4
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 greenCreated: 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 PEOCreated: 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
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
mitochondrial myopathy
Publications
Publications for gene: SLC25A4 were set to PMID:25732997; 27693233
Phenotypes for gene: SLC25A4 were changed from itochondrial myopathy; Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD 617184; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 60928 to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, OMIM:617184
Phenotypes for gene: SLC25A4 were changed from Mitochondrial myopathy; 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 to itochondrial myopathy; Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD 617184; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 60928
Phenotypes for gene: SLC25A4 were changed from mitochondrial myopathy; 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 to Mitochondrial myopathy; 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
Phenotypes for gene: SLC25A4 were changed from mitochondrial myopathy to mitochondrial myopathy; 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
This gene has been classified as Green List (High Evidence).
Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team. Participants who are offered this panel will automatically be offered the following three panels: 1) Congenital muscular dystrophy 2) Congenital myasthenia and 3) Paediatric motor neuronopathy as this will cover a large range of differentials for a weak infant, for where the strict inclusion criteria are not applicable in view of the availability of muscle biopsy testing in peripheral paediatric units.
This gene has been classified as Green List (High Evidence).
Publications for SLC25A4 were set to PMID:25732997; 27693233
This gene has been classified as Green List (High Evidence).
Mode of inheritance for SLC25A4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SLC25A4 was created by ellenmcdonagh
SLC25A4 was added to Congenital myopathypanel. Sources: Literature