Expanding the spectrum of TNNC2 variants in neonatal hypotonia - a family report of a homozygous loss of function.

Abstract

The TNNC2 gene is crucial for skeletal muscle function, and pathogenic variants have been linked to congenital myopathies characterized by hypotonia, muscle weakness, and respiratory insufficiency. To date, TNNC2-related myopathies have been associated only with autosomal dominant missense variants. We report here the first family case of a recessive form of myopathy related to TNNC2. We identified the homozygous splice variant TNNC2(NM_003279.3):c.314 + 1G > C p.(?) in two siblings with a severe clinical presentation, resulting in one neonatal death and one medical termination of pregnancy. This variant induces a splicing defect that leads to a complete loss of the TNNC2 physiological transcript. This case expands the spectrum of TNNC2 variants with a late-onset fetal loss. To the best of our knowledge, this is the first case reporting a recessive form of severe neonatal hypotonia due to TNNC2 variant.