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Paediatric or syndromic cardiomyopathy

Gene: CRLS1

Amber List (moderate evidence)

CRLS1 (cardiolipin synthase 1)
EnsemblGeneIds (GRCh38): ENSG00000088766
EnsemblGeneIds (GRCh37): ENSG00000088766
OMIM: 608188, Gene2Phenotype
CRLS1 is in 6 panels

1 review

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

Comment on list classification: This gene should be rated AMBER as there are two cases with cardiac defects and they harbour the same homozygous variant. In addition, functional studies from patient fibroblasts showed that these variants impair mitochondrial function.
Created: 1 Mar 2023, 8:06 p.m. | Last Modified: 1 Mar 2023, 8:06 p.m.
Panel Version: 2.8
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.

Of these, patient from family 1 had left ventricular noncompaction and biventricular systolic dysfunction, as diagnosed by echocardiogram at 2 days of life, which evolved to hypertrophic cardiomyopathy by 7 weeks of age. The ECG of second patient from family 2 (patient II:3) demonstrated evere biventricular dysfunction, which subsequently improved, while the other patient from the same family with the variant did not exhibit any cardiac phenotype./

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. This patient did not show any cardiac phenotype.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Created: 1 Mar 2023, 8:04 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Combined oxidative phosphorylation deficiency 57, OMIM:620167



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Literature
  • Combined oxidative phosphorylation deficiency 57, OMIM:620167
Clinvar variants
Variants in CRLS1
Panels with this gene

History Filter Activity

1 Mar 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: crls1 has been classified as Amber List (Moderate Evidence).

1 Mar 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

gene: CRLS1 was added gene: CRLS1 was added to Cardiomyopathies - including childhood onset. 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 AMBER