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Mitochondrial disease

Gene: APOO

Amber List (moderate evidence)

APOO (apolipoprotein O)
EnsemblGeneIds (GRCh38): ENSG00000184831
EnsemblGeneIds (GRCh37): ENSG00000184831
OMIM: 300753, Gene2Phenotype
APOO is in 2 panels

3 reviews

Karina Sandoval (Victorian Clinical Genetics Services)

I don't know

PMID: 37649161
1 family, 2 individuals (male & female) with same NMD variant c.532G>T (p.E178*), maternally inherited (mother unaffected).

Both died before 18 months of age with partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies.
Other phenotypes included partial syndactyly of the 2nd and 3rd toes, wrinkled palm, and sole skin.

Functional studies included site directed mutagenesis. This mutation resulted in a highly unstable and degradation
prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and
interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells.
Created: 7 Sep 2023, 2:54 a.m. | Last Modified: 7 Sep 2023, 2:54 a.m.
Panel Version: 0.889

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
agenesis of the corpus callosum; bilateral congenital cataract; hypothyroidism; severe immune deficiencies

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

- PMID: 32439808 (2021) - Three generation family with c.350T>C variant in APOO, encoding a component of the MICOS complex which plays a role in maintaining inner mitochondrial membrane architecture.
Phenotypes include fatigue and muscle weakness (6/8), learning difficulties and cognitive impairment (4/8), and increased blood lactate (2/8). Four individuals were asymptomatic carriers, including one male (authors indicate variability in female carriers was due to skewed X-inactivation, although skewing studies were inconclusive in some cases). Variability in clinical presentation suggests reduced penetrance or possible contribution of additional factors.
Functional studies showed altered MICOS assembly and abnormalities in mitochondria ultrastructure in patient-derived fibroblasts. Knockdown studies in Drosophila and yeast demonstrated mitochondrial structural and functional deficiencies.
Sources: Literature
Created: 3 Mar 2021, 2:09 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mitochondrial disease, MONDO:0044970, APOO-related; Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour

Publications

Arina Puzriakova (Genomics England)

Red List (low evidence)

- PMID: 32439808 (2021) - Three generation family with c.350T>C variant in APOO, encoding a component of the MICOS complex which plays a role in maintaining inner mitochondrial membrane architecture.
Phenotypes include fatigue and muscle weakness (6/8), learning difficulties and cognitive impairment (4/8), and increased blood lactate (2/8). Four individuals were asymptomatic carriers, including one male (authors indicate variability in female carriers was due to skewed X-inactivation, although skewing studies were inconclusive in some cases). Variability in clinical presentation suggests reduced penetrance or possible contribution of additional factors.
Functional studies showed altered MICOS assembly and abnormalities in mitochondria ultrastructure in patient-derived fibroblasts. Knockdown studies in Drosophila and yeast demonstrated mitochondrial structural and functional deficiencies.
Sources: Literature
Created: 2 Mar 2021, 3:32 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Mitochondrial disease, MONDO:0044970, APOO-related
  • Developmental delay
  • Lactic acidosis
  • Muscle weakness
  • Hypotonia
  • Repetitive infections
  • Cognitive impairment
  • Autistic behaviour
OMIM
300753
Clinvar variants
Variants in APOO
Penetrance
None
Publications
Panels with this gene

History Filter Activity

7 Sep 2023, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: APOO were changed from Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour to Mitochondrial disease, MONDO:0044970, APOO-related; Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour

7 Sep 2023, Gel status: 2

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: APOO were set to 32439808

3 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: apoo has been classified as Amber List (Moderate Evidence).

3 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: apoo has been classified as Amber List (Moderate Evidence).

3 Mar 2021, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: APOO was added gene: APOO was added to Mitochondrial disease. Sources: Literature Mode of inheritance for gene: APOO was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: APOO were set to 32439808 Phenotypes for gene: APOO were set to Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour Review for gene: APOO was set to AMBER