Mitochondrial disorders
Gene: SPATA5Comment on list classification: There are sufficient cases to promote this gene to Green at the next GMS panel update. Patients display a phenotype that resembles a mitochondrial disorder and functional studies on patient-derived cells have demonstrated an impact on mitochondrial function, further supporting inclusion of SPATA5 on this panel.Created: 12 Mar 2024, 4:24 p.m. | Last Modified: 12 Mar 2024, 4:24 p.m.
Panel Version: 4.162
Added new-gene-name tag, new approved HGNC gene symbol for SPATA5 is AFG2A.Created: 16 Oct 2023, 6:19 p.m. | Last Modified: 16 Oct 2023, 6:19 p.m.
Panel Version: 4.99
At least five cases with biallelic variants had a clinical presentation resembling a mitochondrial disorder. Functional assays showed SPATA5-deficient neurons had a significant imbalance in the mitochondrial fusion-fission rate, impaired energy production and short axons.Created: 23 Mar 2020, 3:44 a.m. | Last Modified: 23 Mar 2020, 3:44 a.m.
Panel Version: 2.5
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epilepsy, hearing loss, and mental retardation syndrome MIM#616577
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: This gene is being rated as amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.Created: 20 Aug 2019, 3:29 p.m. | Last Modified: 20 Aug 2019, 3:29 p.m.
Panel Version: 1.479
Greater than 15 families have been identified in multiple publications showing that patients with SPATA5 biallelic variants present with intellectual disability, epilepsy, microcephaly and hearing loss, as well as cortical blindness, spasticity and feeding problems; and prior to the gene being discovered to cause the phenotype in these families patients were often thought to have a mitochondrial disorder.
As per Puusepp et al (PMID: 29343804) functional studies were performed on rat cortical neurons. "SPATA5-deficient neurons had a significant imbalance in the mitochondrial fusion-fission rate, impaired energy production and short axons. In conclusion, SPATA5 protein has an important role in mitochondrial dynamics and axonal growth. Biallelic variants in the SPATA5 gene can affect mitochondria in cortical neurons and should be considered in patients with a neurodegenerative disorder and/or with clinical presentation resembling a mitochondrial disorder."
Sources: LiteratureCreated: 19 Aug 2019, 3:52 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epilepsy, hearing loss, and mental retardation syndrome 616577
Publications
Tag Q1_24_promote_green tag was added to gene: SPATA5.
Publications for gene: SPATA5 were set to 27246907; 29343804; 26299366; 28293831
Gene: spata5 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Tag new-gene-name tag was added to gene: SPATA5.
Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366
Gene: spata5 has been classified as Amber List (Moderate Evidence).
gene: SPATA5 was added gene: SPATA5 was added to Mitochondrial disorders. Sources: Literature Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPATA5 were set to PMID: 27246907; 29343804; 26299366 Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome 616577 Penetrance for gene: SPATA5 were set to Complete Review for gene: SPATA5 was set to GREEN