Mitochondrial disorders

Gene: SQOR

Green List (high evidence)

This gene has been rated green on R356 Mitochondrial disorder with complex IV deficiency panel (https://panelapp.genomicsengland.co.uk/panels/537/gene/SQOR/) and hence should be added with green rating on this panel.

PMID:32160317 reported two Hutterite siblings with encephalopathy and Leigh syndrome-like brain lesions and they were identified with a homozygous missense variant (c.637G > A/ p.(Glu213Lys)) in SQOR gene. This variant was identified as a founder variant in the Lehrerleut Hutterite with a carrier frequency of 1 in 13. In one of the siblings, SQOR enzyme function was reduced in liver and muscle tissue, and the function of complex IV of the mitochondrial respiratory chain was reduced in muscle tissue, whereas the content and assembly of complex IV was normal.

This publication also reported a boy of Turkish descent with encephalopathy and Leigh syndrome-like brain lesions and identified with a 1-bp deletion variant in this gene (c.446delT). This patient had 2 asymptomatic sisters who were also homozygous for the variant, suggesting partial segregation of the variant. The patient had severely reduced fibroblast SQOR enzyme activity and protein levels.

This gene has been associated with relevant phenotype in OMIM (MIM #619221).

Created: 6 Jun 2025, 8:39 a.m. | Last Modified: 6 Jun 2025, 8:39 a.m.

Panel Version: 9.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sulfide:quinone oxidoreductase deficiency, OMIM:619221

Publications

• 32160317

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval

Created: 3 Mar 2022, 2:09 p.m. | Last Modified: 3 Mar 2022, 2:09 p.m.

Panel Version: 1.13

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 26 Jan 2021, 3:12 p.m. | Last Modified: 26 Jan 2021, 3:12 p.m.

Panel Version: 1.7

Not associated with relevant phenotype in OMIM or in Gen2Phen. At least 2 variants reported in unrelated cases, together with supportive functional studies. The authors of PMID 32160317 hypothesise that in their patients, the low residual SQOR activity was likely sufficient to support H2S clearance during stable episodes but was insufficient during acute illness with catabolism resulting in H2S accumulation and toxicity. They conclude that "SQOR deficiency represents a new, potentially treatable, cause of Leigh disease".

Created: 26 Jan 2021, 3:07 p.m. | Last Modified: 26 Jan 2021, 3:10 p.m.

Panel Version: 1.6

I don't know

Requires review for GMS - should this be considered a primary mitochondrial disorder?
Sources: Literature

Created: 24 Jan 2021, 4:52 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome

Publications

• PMID: 32160317