Rhabdomyolysis and Metabolic Myopathy
Gene: ASPH
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: LiteratureCreated: 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
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
Gene: asph has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Gene: asph has been classified as Amber List (Moderate Evidence).
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