Congenital myopathy

Gene: TRDN

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 10:39 a.m. | Last Modified: 26 Sep 2024, 10:39 a.m.

Panel Version: 4.42

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

• 25922419
• 28202702
• 30649896

Green List (high evidence)

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

• PMID:25922419
• 28202702
• 30649896

Mode of pathogenicity
Other

I don't know

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 list

Created: 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

• 25922419
• 28202702