Mitochondrial disorders

Gene: CRLS1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 9:52 a.m. | Last Modified: 11 Oct 2023, 9:52 a.m.

Panel Version: 4.95

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: This gene should be rated GREEN as it has been associated with mitochondrial disorders, as identified from three unrelated cases, and supported by functional evidence.

Created: 1 Mar 2023, 7:31 p.m. | Last Modified: 1 Mar 2023, 7:32 p.m.

Panel Version: 3.12

Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature

Created: 1 Mar 2023, 7:28 p.m. | Last Modified: 1 Mar 2023, 9:02 p.m.

Panel Version: 3.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 57, OMIM:620167

Publications

• 35147173