Likely inborn error of metabolism - targeted testing not possible
Gene: CRLS1
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
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: LiteratureCreated: 2 Mar 2023, 6:39 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency 57, OMIM:620167
Publications
Tag Q1_23_promote_green was removed from gene: CRLS1.
Source NHS GMS was added to CRLS1. Source Expert Review Green was added to CRLS1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: crls1 has been classified as Amber List (Moderate Evidence).
Gene: crls1 has been classified as Amber List (Moderate Evidence).
Gene: crls1 has been classified as Amber List (Moderate Evidence).
Tag Q1_23_promote_green tag was added to gene: CRLS1.
Gene: crls1 has been classified as Amber List (Moderate Evidence).
gene: CRLS1 was added gene: CRLS1 was added to Inborn errors of metabolism. Sources: Literature Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CRLS1 were set to 35147173 Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167 Review for gene: CRLS1 was set to GREEN