For once, a heterozygous variant of the TTN gene can lead to a dominant myopathy

The 14 members (eight affected and six healthy) of a family with autosomal dominant myopathy were examined in detail:

• the patients presented the same picture of skeletal muscle damage associated with cardiac damage;
• genetic analysis revealed a nonsense variant c.70051C>Tp.(Arg23351) in the TTN gene;
• RNA sequencing showed reduced expression of the mutated allele and Western blot analysis revealed a truncated titin of compatible size.

 

A Titin Truncating Variant Causing a Dominant Myopathy With Cardiac Involvement in a Large Family: The Exception That Proves the Rule. Claeys KG, Savarese M, Jonson PH et al. Neurol Genet. 2024 Aug 12;10(5):e200185.