Likely inborn error of metabolism - targeted testing not possible
Gene: ATP5A1
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 10:24 a.m. | Last Modified: 1 Feb 2023, 10:24 a.m.
Panel Version: 3.6
This gene was recently included on a gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) on behalf of GMS Mitochondrial providers, indicating that the rating should be upgraded from Amber to Green on Mitochondrial panels (R357 and R63). Two families (with two affected sibs each) reported with recessive variants and supported by functional studies (PMIDs: 23599390; 23596069). Six unrelated patients have been reported with heterozygous variants; including one recurrent variant c.620G>A in four cases, c.545G>A and c.1037C>T in the remaining two, respectively (PMIDs: 34483339; 34954817). The MOI has been updated from biallelic to both mono- and biallelic inline with published cases. Overall there is sufficient evidence to promote this gene to Green status at the next GMS panel update.Created: 30 Aug 2022, 9:08 a.m. | Last Modified: 30 Aug 2022, 9:08 a.m.
Panel Version: 2.265
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4, OMIM: 615228; Combined oxidative phosphorylation deficiency 22, OMIM: 616045
Publications
Added new-gene-name tag, new approved HGNC gene symbol for ATP5A1 is ATP5F1ACreated: 9 May 2019, 2:59 p.m.
Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys mentioned in this article have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.Created: 22 Aug 2019, 10:01 a.m. | Last Modified: 27 Sep 2019, 3:07 p.m.
Panel Version: 1.311
Comment on list classification: No additional variants have been reported to date.Created: 30 Apr 2019, 10:26 a.m.
Comment on publications: PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency);PMID: 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).Created: 30 Apr 2019, 10:25 a.m.
Comment on list classification: Kept as red, as each phenotype association has only been reported in one family - as indicated by reviewer's comment.Created: 26 Feb 2016, 12:40 p.m.
single report in literature - two affected siblingsCreated: 3 Feb 2016, 6 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Tag Q3_22_rating was removed from gene: ATP5A1.
Source Expert Review Green was added to ATP5A1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: ATP5A1 were set to PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency); PMID: 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).
Phenotypes for gene: ATP5A1 were changed from ?Combined oxidative phosphorylation deficiency 22; Complex V (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4; ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4 615228; ?Combined oxidative phosphorylation deficiency 22 616045 to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4, OMIM: 615228; Combined oxidative phosphorylation deficiency 22, OMIM: 616045
Tag Q3_22_MOI was removed from gene: ATP5A1. Tag Q3_22_rating tag was added to gene: ATP5A1.
Tag Q3_22_MOI tag was added to gene: ATP5A1.
Mode of inheritance for gene: ATP5A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Tag new-gene-name tag was added to gene: ATP5A1.
Source NHS GMS was added to ATP5A1. Source London North GLH was added to ATP5A1.
Sarah Leigh: Associated with phenotype in O
Added phenotypes ?Combined oxidative phosphorylation deficiency 22; ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4 for gene: ATP5A1 Publications for gene ATP5A1 were changed from 27604308 to PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency); PMID: 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).
gene: ATP5A1 was added gene: ATP5A1 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: ATP5A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP5A1 were set to 27604308 Phenotypes for gene: ATP5A1 were set to Complex V (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4 615228; ?Combined oxidative phosphorylation deficiency 22 616045