A novel mutation in the COL12A1 gene

Abstract

Mutations in collagen XII have been recently described to cause modifications in the connective tissue which phenotypic demonstration resembles that of collagen VI related myopathies. We describe a Caucasian 14-year old girl who complained to her doctor about not being able to practice schools' sports due to recurrent clavicle dislocation when trying to throw a ball. In addition, when questioned, she also reported a notion of lower strength in the upper limbs when compared to same age peers. Based on the clinical exam performed, a joint hypermobility with a slight reduction of the muscular strength of the upper limbs diagnosis was noted. Targeted sequencing identified a heterozygous missense mutation in COL12A1 - c.8336G > A (p. Arg2779His). Algorithms developed to predict the effect of the changes on the protein structure and function do not agree on the potential impact of this modification. This case shows the importance to consider collagen XII-related disorders when in presence of patients with an overlapping phenotype with both muscle and connective tissue abnormalities, once mutations in collagen VI have been excluded.

Keywords: Collagen XII mutation; Congenital pes equinovarus; Connective tissue; Joints’ hyperlaxity.