| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Congenital Myasthenia v2.4 | DES | Bryony Thompson Marked gene: DES as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Myasthenia v2.4 | DES | Bryony Thompson Gene: des has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Myasthenia v2.4 | DES | Bryony Thompson Classified gene: DES as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Myasthenia v2.4 | DES | Bryony Thompson Gene: des has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Myasthenia v2.3 | DES |
Bryony Thompson gene: DES was added gene: DES was added to Congenital Myasthenia. Sources: Literature Mode of inheritance for gene: DES was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DES were set to 37721175; 29395675 Phenotypes for gene: DES were set to congenital myasthenic syndrome MONDO:0018940 Review for gene: DES was set to AMBER Added comment: PMID 29395675 reports two individuals from one family (cousins) with a homozygous truncating DES variant c.345dupC presenting with fatigable weakness, ocular involvement and cardiomyopathy; PMID 37721175 reports three unrelated individuals from three families with a homozygous intronic splice‑site DES variant c.1023+5G>A presenting with limb‑girdle weakness, oculo‑bulbar involvement, elevated CK and a neuromuscular‑junction defect. Both studies describe a recessive congenital myasthenic syndrome caused by loss‑of‑function DES variants, a monogenic disorder amenable to targeted therapies, aligning with the Congenital Myasthenia panel’s focus on fatigable weakness and hypotonia. Sources: Literature |
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| Congenital Myasthenia v2.1 | TEFM |
Bryony Thompson gene: TEFM was added gene: TEFM was added to Congenital Myasthenia. Sources: Literature Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TEFM were set to 37721175; 36823193 Phenotypes for gene: TEFM were set to combined oxidative phosphorylation deficiency 58, MONDO:0957537 Review for gene: TEFM was set to GREEN Added comment: PMID 36823193 reports seven individuals from five unrelated families with biallelic TEFM loss‑of‑function variants and a congenital myasthenic‑syndrome‑like mitochondrial disease; PMID 37721175 likely reports the same two affected siblings from an Indian family homozygous for the same p.Pro157Ala variant. Across five families, the phenotype includes fatigable muscle weakness, ptosis, ophthalmoparesis, limb‑girdle weakness and variable neurological features such as epilepsy and ataxia. Functional studies demonstrate reduced TEFM protein, impaired mitochondrial transcription, decreased complex I activity and neuromuscular junction defects in zebrafish, supporting a loss‑of‑function mechanism. Sources: Literature |
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