Congenital myopathy
Gene: TRDN
Comment on list classification: As reviewed by Anna Sarkozy (Great Ormond Street Hospital), there is sufficient evidence (9 unrelated cases) for promoting this gene to Green at the next major review.Created: 26 Apr 2023, 1:04 p.m. | Last Modified: 26 Apr 2023, 1:04 p.m.
Panel Version: 4.29
PMID:25922419 reported that two of the five children (families 2 & 5) identified with recessive variants in TRDN gene had mild to moderate skeletal muscle weakness.
PMID:28202702 reported a six-year-old boy with lifelong muscle weakness, who was identified with compound heterozygous null variants in TRDN gene that was suspected of skeletal muscle involvement.
Mild skeletal myopathy/proximal muscle weakness was also noted in six out of 21 (29%) patients in the International Triadin Knockout Syndrome Registry reported in PMID:30649896.Created: 26 Apr 2023, 1:02 p.m. | Last Modified: 26 Apr 2023, 1:02 p.m.
Panel Version: 4.27
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, OMIM:615441
Publications
as previously indicated, recessive frameshift mutations, leading to loss of TRDN, were found to cause a skeletal myopathy in a subset of patients with triadin knockout syndrome. Altman et al describe that A 2 of the 5 patients displayed mild skeletal muscle weakness. A recent publication on a registry of 21 patients with TRDN gene variants indicate that mild skeletal myopathy/proximal muscle weakness was noted in 6 (29%) patients. . Alternative splicing of triadin mRNA results in tissue-specific isoforms of triadin found in both cardiac and skeletal muscle. all of the mutations discovered to date resulting in cardiac triadin null status also result in patients being skeletal muscle triadin null. it has been highligthed that it is possible that we are underestimating the number of patients with a skeletal myopathy associated with TRDN variants because of the fact that the phenotype is mild and pateints are mostly ascertained by genetic cardiologists and most of these patients have not been evaluated by a neuromuscular specialist.in view of this and previous evidences, we would recommend upgrade to green.Created: 11 Feb 2023, 9:25 a.m. | Last Modified: 11 Feb 2023, 9:25 a.m.
Panel Version: 3.124
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
skeletal myopathy
Publications
Mode of pathogenicity
Other
Comment on list classification: Amber gene recommended by Anna Sarkozy as a result of GLH Test Group prior to sign off.Created: 4 Dec 2019, 1:15 p.m. | Last Modified: 4 Dec 2019, 1:15 p.m.
Panel Version: 1.210
gene recommended to be added to panel by Anna Sarkozy as a result of GLH Test Group prior to sign off. Recessive frameshift mutations, leading to loss of TRDN, were found to cause a skeletal myopathy in a subset of patients with triadin knockout syndrome.
Altmann HM, Tester DJ, Will ML, et al. : Homozygous/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest: Elucidation of the Triadin Knockout Syndrome. Circulation. 2015;131(23):2051–60. 10.1161/CIRCULATIONAHA.115.015397
Engel AG, Redhage KR, Tester DJ, et al. : Congenital myopathy associated with the triadin knockout syndrome. Neurology. 2017;88(12):1153–6.
Sources: Expert listCreated: 4 Dec 2019, 1:15 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441
Publications
Tag Q2_23_NHS_review tag was added to gene: TRDN.
Tag Q2_23_promote_green tag was added to gene: TRDN.
Gene: trdn has been classified as Amber List (Moderate Evidence).
Publications for gene: TRDN were set to 25922419; 28202702
Phenotypes for gene: TRDN were changed from Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441 to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, OMIM:615441
Source NHS GMS was added to TRDN.
Gene: trdn has been classified as Amber List (Moderate Evidence).
gene: TRDN was added gene: TRDN was added to Congenital myopathy. Sources: Expert list Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRDN were set to 25922419; 28202702 Phenotypes for gene: TRDN were set to Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441 Review for gene: TRDN was set to AMBER