Mitochondrial disorders

Gene: MARS2

Green List (high evidence)

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

I don't know

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

I don't know

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

• 25754315

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.

Green List (high evidence)