Mitochondrial disorders
Gene: MARS2
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green.
Comment from GMS reviewers: If AR spastic ataxia cases due to rearrangement/duplication variants are included this is a green gene (NT), There looks to be sufficient evidence - include spastic ataxia OMIM #611390(C&S)Created: 1 Feb 2023, 12:16 p.m. | Last Modified: 1 Feb 2023, 12:41 p.m.
Panel Version: 3.6
In response to Zornitza Stark's (Australian Genomics), review 20 Mar 2020: which questions if there is sufficient evidence for both Combined oxidative phosphorylation deficiency 25 (OMIM:616430) and Spastic ataxia 3, autosomal recessive (OMIM:611390) to be green on this panel, based on copy number variants in three families with Spastic ataxia 3, autosomal recessive (OMIM:611390)(PMID: 22448145) and Combined oxidative phosphorylation deficiency 25 (OMIM:616430)(PMID: 25754315) in one family who was compound heterozygous for a missense and a terminating variant. No other variants appear to have been reported in the literature to date.Created: 23 May 2022, 1:58 p.m. | Last Modified: 23 May 2022, 2:03 p.m.
Panel Version: 2.105
1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV.
The spastic ataxia phenotype is later-onset and caused by complex rearrangements rather than SNVs. I am not sure the two can be lumped together for the purpose of gene-disease association assessment at this stage.Created: 20 Mar 2020, 10:05 a.m. | Last Modified: 20 Mar 2020, 10:05 a.m.
Panel Version: 2.5
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency 25, OMIM #616430; Spastic ataxia 3, autosomal recessive, OMIM #611390
Publications
Missense variants in this gene reported for Combined oxidative phosphorylation deficiency 25.Created: 30 Nov 2016, 10:14 a.m.
Comment on mode of inheritance: Confirmed on OMIM.Created: 15 Mar 2016, 8:36 a.m.
Comment on list classification: Two reviewers suggesting that this gene should be green: Carl Fratter also suggests this should be green, therefore promoted from red to green.Created: 15 Mar 2016, 8:36 a.m.
Tag Q2_22_rating was removed from gene: MARS2. Tag Q2_22_expert_review was removed from gene: MARS2.
Tag missense was removed from gene: MARS2. Tag Q2_22_rating tag was added to gene: MARS2. Tag Q2_22_expert_review tag was added to gene: MARS2.
Publications for gene: MARS2 were set to PMID: 22448145; 25754315
Victorian Clinical Genetics Services was added to MARS2. Panel: Mitochondrial disorders
This gene has been classified as Green List (High Evidence).
Phenotypes for MARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Spastic Ataxia 13, autosomal recessive, 611390; ?Combined oxidative phosphorylation deficiency 25
Publications for MARS2 were set to PMID: 22448145; 25754315
Mode of inheritance for MARS2 was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
MARS2 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert,Expert list,Radboud University Medical Center, Nijmegen
MARS2 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert,Expert list,Radboud University Medical Center, Nijmegen
MARS2 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert,Expert list,Radboud University Medical Center, Nijmegen