Congenital myopathy
Gene: RYR1
Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.Created: 30 Apr 2019, 10:09 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600
Publications
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600
Publications
Comment when marking as ready: Clear evidence of causation. AD and AR inheritanceCreated: 3 Feb 2017, 11:18 a.m.
Comment on mode of inheritance: Caution re malignant hyperthermia susceptibility (even in unaffected carriers). Potentially actionableCreated: 3 Feb 2017, 11:17 a.m.
Comment on list classification: RYR1 a recognised cause of central core disease. Tagged as pharmacogenetic / treatable in view of the need to highlight risk of MHS (malignant hyperthermia susceptibility) in affected individuals and potentially unaffected carriersCreated: 3 Feb 2017, 11:16 a.m.
Well established causal role with congenital myopathy associated with central cores. AR or AD inheritance. Important to recognise that phenotype of RYR1 mutations can also include Malignant Hyperthermia susceptibility, which could also be of clinical relevance to healthy carriers where AR inheritance is relevant within the family.Created: 30 Jan 2017, 11:27 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000
Publications
Phenotypes for gene: RYR1 were changed from Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600 to Central core disease, OMIM:117000; Neuromuscular disease, congenital, with uniform type 1 fiber, OMIM:117000; Minicore myopathy with external ophthalmoplegia, OMIM:255320; King-Denborough syndrome, OMIM:619542
Source NHS GMS was added to RYR1.
Source London South GLH was added to RYR1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team. Participants who are offered this panel will automatically be offered the following three panels: 1) Congenital muscular dystrophy 2) Congenital myasthenia and 3) Paediatric motor neuronopathy as this will cover a large range of differentials for a weak infant, for where the strict inclusion criteria are not applicable in view of the availability of muscle biopsy testing in peripheral paediatric units.
This gene has been classified as Green List (High Evidence).
Phenotypes for RYR1 were set to Central core disease 117000; Minicore myopathy with external ophthalmoplegia 255320; Neuromuscular disease, congenital, with uniform type 1 fiber 117000; Malignant hyperthermia susceptibility 1 145600
Publications for RYR1 were set to 26799446
Mode of inheritance for RYR1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
RYR1 was added to Congenital myopathypanel. Sources: Expert
RYR1 was added to Congenital myopathypanel. Sources: Radboud University Medical Center, Nijmegen
RYR1 was added to Congenital myopathypanel. Sources: UKGTN