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| Malignant Hyperthermia Susceptibility v1.3 | ASPH |
Paul De Fazio gene: ASPH was added gene: ASPH was added to Malignant Hyperthermia Susceptibility. 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 Added comment: 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 |
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| Malignant Hyperthermia Susceptibility v0.11 | TRPV1 | Bryony Thompson changed review comment from: 3 cases with a muscle biopsy sensitive for halothane but not for caffeine, MHSh, and a single case susceptible to both (MHS). One of the MHSh cases was from a family with RYR1-associated myopathy, where the TRPV1 occurred with RYR1 variants. Two of the cases had a clinical diagnosis of malignant hyperthermia and two of the cases had an exertional heat stress episode. Supporting functional assays in HEK293 cells and trpv1 -/- mouse muscle, demonstrated impairment of intracellular Ca2+ signaling.; to: 3 cases with a muscle biopsy sensitive for halothane but not for caffeine, MHSh, and a single case susceptible to both (MHS). One of the MHSh cases was from a family with RYR1-associated myopathy, where the TRPV1 occurred with RYR1 variants. Two of the cases had a clinical diagnosis of malignant hyperthermia and two of the cases had an exertional heat stroke episode. Supporting functional assays in HEK293 cells and trpv1 -/- mouse muscle, demonstrated impairment of intracellular Ca2+ signaling. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant Hyperthermia Susceptibility v0.4 | RYR1 | Bryony Thompson edited their review of gene: RYR1: Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant Hyperthermia Susceptibility v0.2 | RYR1 | Bryony Thompson Marked gene: RYR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant Hyperthermia Susceptibility v0.2 | RYR1 | Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant Hyperthermia Susceptibility v0.2 | RYR1 | Bryony Thompson Classified gene: RYR1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant Hyperthermia Susceptibility v0.2 | RYR1 | Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant Hyperthermia Susceptibility v0.1 | RYR1 |
Bryony Thompson gene: RYR1 was added gene: RYR1 was added to Malignant Hyperthermia Susceptibility. Sources: Expert list Mode of inheritance for gene: RYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RYR1 were set to 20301325 Phenotypes for gene: RYR1 were set to {Malignant hyperthermia susceptibility 1} MIM#145600 Mode of pathogenicity for gene: RYR1 was set to Other Review for gene: RYR1 was set to GREEN Added comment: Gain-of-function RYR1 variants are the most common cause of malignant hyperthermia Sources: Expert list |
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