Likely inborn error of metabolism

Gene: CRLS1

Green List (high evidence)

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

Created: 11 Oct 2023, 12:32 p.m. | Last Modified: 11 Oct 2023, 12:32 p.m.

Panel Version: 4.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).

Created: 2 Mar 2023, 6:43 a.m. | Last Modified: 2 Mar 2023, 6:43 a.m.

Panel Version: 3.10

Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).

Created: 2 Mar 2023, 6:43 a.m. | Last Modified: 2 Mar 2023, 6:43 a.m.

Panel Version: 3.10

Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).

Created: 2 Mar 2023, 6:43 a.m. | Last Modified: 2 Mar 2023, 6:43 a.m.

Panel Version: 3.9

Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).

Created: 2 Mar 2023, 6:42 a.m. | Last Modified: 2 Mar 2023, 6:42 a.m.

Panel Version: 3.9

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.

Lipidomics in fibroblasts from 2 patients demonstrated that cardiolipin was reduced, cardiolipin acyl side chains had an abnormal distribution, and substrates of CRLS1 were abnormally elevated, including an elevation of phosphatidylglycerol.
Sources: Literature

Created: 2 Mar 2023, 6:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 57, OMIM:620167

Publications

• 35147173