Congenital myopathy
Gene: DNM2The "watchlist_moi" tag is added to this gene to review the MOI in light of any new evidence as there is one family reported with biallelic inheritance.Created: 3 Apr 2023, 6:14 p.m. | Last Modified: 3 Apr 2023, 6:14 p.m.
Panel Version: 4.18
Biallelic variants in DNM2 gene was only reported in three siblings, born of consanguineous Pakistani parents and not from any unrelated patients. These siblings presented with Lethal congenital contracture syndrome 5 (MIM #615368) characterised by akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. Muscle biopsy and EMG showed myopathic features. Therefore, the MOI should be left as "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" until more cases with biallelic variants are reported.Created: 3 Apr 2023, 6:10 p.m. | Last Modified: 3 Apr 2023, 6:10 p.m.
Panel Version: 4.15
Phenotypes
Lethal congenital contracture syndrome 5, OMIM:615368
Publications
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
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482
Publications
Variants in this GENE are reported as part of current diagnostic practice
biallelic DNM2 variants were also described in three consanguineous patients with lethal congenital syndrome caractherised by akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. muscle biopsy and EMG showed myopathic features. in particular, muscle biopsy of one patient showed small rounded fibers with some centralized nuclei, suggestive of a congenital myopathy whereas biopsy of a 2nd patient showed atrophic fibers without obvious centralization of nuclei.Created: 24 Mar 2023, 11:39 a.m. | Last Modified: 24 Mar 2023, 11:39 a.m.
Panel Version: 4.2
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482; lethal congenital syndrome
Publications
Comment when marking as ready: Missense mutations reported in both phenotypes (centronuclear myopathy and CMT)Created: 2 Feb 2017, 11:41 a.m.
Many reported families / mutations. Only missense in centronuclear myopathy but one frameshift found in relation to CMT presentation. The majority appear to present in childhood / early adulthood but specific mutations p.Ala618Thr and p.Ser619Trp/Leu present in neonatal phase therefore appropriate for congenital panel.Created: 26 Jan 2017, 10:38 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Myopathy, centronuclear 160150
Publications
Tag watchlist_moi tag was added to gene: DNM2.
Phenotypes for gene: DNM2 were changed from Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368 to Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368
Phenotypes for gene: DNM2 were changed from Centronuclear myopathy 1, OMIM:160150 to Centronuclear myopathy 1, OMIM:160150; Lethal congenital contracture syndrome 5, OMIM:615368
Publications for gene: DNM2 were set to 22396310
Phenotypes for gene: DNM2 were changed from Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482 to Centronuclear myopathy 1, OMIM:160150
Publications for gene: DNM2 were set to 22396310; 15689448
Publications for gene: DNM2 were set to 22396310
Source NHS GMS was added to DNM2.
Source London South GLH was added to DNM2. 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 DNM2 were set to Myopathy, centronuclear, 160150; Charcot-Marie-Tooth disease, axonal, type 2M, 606482
Publications for DNM2 were set to 22396310
DNM2 was added to Congenital myopathypanel. Sources: Expert
DNM2 was added to Congenital myopathypanel. Sources: Radboud University Medical Center, Nijmegen
DNM2 was added to Congenital myopathypanel. Sources: UKGTN
DNM2 was added to Congenital myopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services