Rhabdomyolysis and Metabolic Myopathy

Gene: ASPH

Amber List (moderate evidence)

ASPH (aspartate beta-hydroxylase)
EnsemblGeneIds (GRCh38): ENSG00000198363
EnsemblGeneIds (GRCh37): ENSG00000198363
OMIM: 600582, Gene2Phenotype
ASPH is in 5 panels

2 reviews

Paul De Fazio (Victorian Clinical Genetics Services)

I don't know

In a study of 103 individuals (63 affected from 34 families, plus 40 sporadic cases) who had either a sentinel event of EHI or MH, or else a positive CHCT and a first degree releative with EHI/MH, and where RYR1 and CACNA1S Sanger sequencing was negative, the following variants in ASPH were identified in unrelated individuals:

- c.161T > C in 2 members of a family with myalgias exacerbated by heat/exercise. One had elevated CK. Both had positive CHCT. An unaffected sibling did not have the variant. 27 hets in gnomad v2 / 17 hets in gnomad v3.
- c.445G>C in a patient with MH, myalgias and muscle cramps worsened by heat and exercise. 4 hets in gnomad v2 / 3 hets in gnomad v3. Non-coding in the MANE transcript.
- c.263A > C in a patient with EHI, diagnosed as MHN by in vitro contracture test. Absent from gnomad but non-coding in the MANE transcript.
- c.605A > G in a patient with EHI, diagnosed as MHN by in vitro contracture test. 223 hets in gnomad v2 / 120 hets in gnomad v3; no homs. Non-coding in the MANE transcript.

A zebrafish model and cell line functional studies supported pathogenicity of the c.161T > C and c.263A > C variants.
Sources: Literature
Created: 14 Jul 2022, 1:35 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Exertional heat illness; malignant hyperthermia susceptibility

Publications

Variants in this GENE are reported as part of current diagnostic practice

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Traboulsi syndrome is characterized by dislocated crystalline lenses and anterior segment abnormalities in association with a distinctive facies involving flat cheeks and a beaked nose. Some affected individuals develop highly unusual nontraumatic conjunctival cysts (filtering blebs), presumably caused by abnormal thinning of the sclera.

At least 3 unrelated families reported.
Created: 6 Dec 2021, 2:53 a.m. | Last Modified: 6 Dec 2021, 2:53 a.m.
Panel Version: 0.10092

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Traboulsi syndrome , MIM#601552

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Exertional heat illness
  • malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
OMIM
600582
Clinvar variants
Variants in ASPH
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Jul 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

14 Jul 2022, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related

14 Jul 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

14 Jul 2022, Gel status: 0

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

Paul De Fazio (Victorian Clinical Genetics Services)

gene: ASPH was added gene: ASPH was added to Rhabdomyolysis. Sources: Literature Mode of inheritance for gene: ASPH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ASPH were set to 35697689 Phenotypes for gene: ASPH were set to Exertional heat illness; malignant hyperthermia susceptibility Review for gene: ASPH was set to AMBER gene: ASPH was marked as current diagnostic