Novel Titin Gene Mutation Causing Autosomal Dominant Limb-Girdle Muscular Dystrophy.

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Titinopathies are a group of inherited muscle disorders caused by mutations in the TTN gene.
• Limb-girdle muscular dystrophy (LGMD) is characterized by progressive muscle weakness and wasting, primarily affecting the shoulders and hips.

Observation:

• A family with autosomal dominant titinopathy presented with limb-girdle muscular dystrophy and contractures.
• Genetic analysis revealed two TTN gene variants: c.712G>C (p.Glu238Gln) and a novel variant c.1397A>C (p.Gln466Arg).

Findings:

• The novel TTN variant c.1397A>C, p.Gln466Arg segregated with the disease in the affected family members.
• Protein modeling indicated that the p.Gln466Arg variant is damaging, suggesting it as the causative mutation for the observed muscular dystrophy.

Implications:

• This research expands the mutational spectrum of titinopathies.
• Identification of novel disease-causing variants aids in genetic diagnosis and understanding of muscular dystrophy pathogenesis.