Mitochondrial disorders
Gene: ATP5A1
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 12:16 p.m. | Last Modified: 1 Feb 2023, 12:16 p.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 other 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: 2.123
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
PMID: 34954817 reports three individuals with de novo monoallelic missense variants. One of these is the recurrent p.(Arg207His) variant while the other two variants are different substitutions. The three patients presented with a variable phenotypes: (1) a 14-year-old girl who presented during the first few months of life with developmental delay, failure-to-thrive, and lactic acidosis. She recovered and had no persistent neurologic phenotype; (2) a 17-year-old boy with psychomotor delay, intellectual disability, ataxia, spastic paraparesis, and dystonia; (3) a 12-year-old girl with psychomotor retardation, spastic tetraparesis, generalized dystonia, absent speech, swallowing problems, and increased blood lactate concentrations. Enzymatic investigations of muscle tissue from patient 1 showed a decrease in ATPase activity.Created: 3 Feb 2022, 10:29 p.m. | Last Modified: 3 Feb 2022, 10:29 p.m.
Panel Version: 2.85
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
feeding intolerance, failure to thrive, hyperammonemia, lactic acidemia
Publications
Comment on list classification: 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 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 a.m. | Last Modified: 22 Aug 2019, 10 a.m.
Panel Version: 1.481
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.
Added new-gene-name tag, new approved HGNC gene symbol is ATP5F1ACreated: 21 Mar 2018, 1:01 p.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 NHS GMS was added to 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 23599390; 23596069
Phenotypes for gene: ATP5A1 were changed from ?Combined oxidative phosphorylation deficiency 22; ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4 to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4, OMIM: 615228; Combined oxidative phosphorylation deficiency 22, OMIM: 616045
Mode of inheritance for gene: ATP5A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q3_22_rating tag was added to gene: ATP5A1.
Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Gene: atp5a1 has been classified as Red List (Low Evidence).
Mode of inheritance for gene: ATP5A1 was changed from to BIALLELIC, autosomal or pseudoautosomal
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).
Victorian Clinical Genetics Services was added to ATP5A1. Panel: Mitochondrial disorders
Publications for 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).
Publications for ATP5A1 were set to PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency); 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Phenotypes for ATP5A1 were set to ?Combined oxidative phosphorylation deficiency 22; ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4
Publications for ATP5A1 were set to PMID: 23599390; 23596069
ATP5A1 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert,Expert list,Radboud University Medical Center, Nijmegen
ATP5A1 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert,Expert list,Radboud University Medical Center, Nijmegen
ATP5A1 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert,Expert list,Radboud University Medical Center, Nijmegen