Rhabdomyolysis and Metabolic Myopathy
Gene: OBSCN
-Six unrelated individuals with severe, recurrent rhabdomyolysis carrying bi-allelic loss of function variants
-Three of six probands experienced acute renal failure
-None presented with cardiac involvement/symptoms of cardiac disease
-Patient muscles demonstrated reduced OBSCN expression and loss of obscurin protein
Sources: LiteratureCreated: 1 Feb 2022, 11:33 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Rhabdomyolysis, MONDO:0005290
Publications
Variants in this GENE are reported as part of current diagnostic practice
Additional evidence to question the pathogenicity of reported variants:
PMID: 33438037 - Fukuzawa et al 2021 - look at protein–protein interactions and protein domain stability, using quantitative biochemical and biophysical approaches on the proposed pathogenic R4344Q variant which is found in 15% of African Americans, along with the previously reported R4444W variant. They find no evidence for a pathogenetic effect.Created: 6 Jul 2021, 12:08 p.m. | Last Modified: 6 Jul 2021, 12:08 p.m.
Panel Version: 0.8229
Publications
Limited evidence by ClinGen working group.
Via ClinGen: 8 probands in 3 publications but only 3 probands from 1 publication were though to have pathogenic variants (others were excluded based on population frequency and expert review).
No additional case reports were found. A mouse model lends some support to the association of this gene with heart disease although not HCM specifically.
Sources: LiteratureCreated: 29 Jul 2020, 6:33 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Hypertrophic cardiomyopathy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: OBSCN were changed from Rhabdomyolysis, MONDO:0005290 to Rhabdomyolysis, MONDO:0005290, OBSCN-related
Gene: obscn has been classified as Green List (High Evidence).
Gene: obscn has been classified as Green List (High Evidence).
gene: OBSCN was added gene: OBSCN was added to Rhabdomyolysis. Sources: Literature Mode of inheritance for gene: OBSCN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OBSCN were set to PMID: 34957489 Phenotypes for gene: OBSCN were set to Rhabdomyolysis, MONDO:0005290 Penetrance for gene: OBSCN were set to unknown Review for gene: OBSCN was set to GREEN gene: OBSCN was marked as current diagnostic