Congenital myopathy

Gene: SLC25A4

Green List (high evidence)

SLC25A4 (solute carrier family 25 member 4)
EnsemblGeneIds (GRCh38): ENSG00000151729
EnsemblGeneIds (GRCh37): ENSG00000151729
OMIM: 103220, Gene2Phenotype
SLC25A4 is in 17 panels

3 reviews

Anna Sarkozy (Great Ormond Street Hospital)

Red List (low evidence)

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

Phenotypes
mitochondrial myopathy

Publications

Helen Brittain (Genomics England Curator)

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

Ellen McDonagh (Genomics England Curator)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mitochondrial myopathy

Publications

History Filter Activity

8 Jan 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

8 Jan 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

8 Jan 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

7 Mar 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

22 Feb 2017, Gel status: 4

panel promoted to version 1

Helen Brittain (Genomics England Curator)

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.

3 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

3 Feb 2017, Gel status: 4

Set publications

Helen Brittain (Genomics England Curator)

Publications for SLC25A4 were set to PMID:25732997; 27693233

3 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

3 Feb 2017, Gel status: 0

Set Mode of Inheritance

Helen Brittain (Genomics England Curator)

Mode of inheritance for SLC25A4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

25 Aug 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SLC25A4 was created by ellenmcdonagh

25 Aug 2016, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC25A4 was added to Congenital myopathypanel. Sources: Literature