The phenotypic spectrum in a patient with Glycine to Serine mutation in the COL2A1 gene: overview study

Objective Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant type II collagenopathies characterized by skeletal dysplasia, short stature, and with vision and auditory defects. In this study, we have investigated in more detail the phenotypic and genotypic characterization resulting from glycine to serine mutations in the COL2A1 gene in a 2-year-old boy. Materials and methods Detailed clinical and radiological phenotypic characterization was the baseline tool to guide the geneticists toward proper genotypic confirmation. Results Genetic analysis revealed a de novo mutation, c.1681G>A (p.Gly561Ser), in the collagen type II alpha-1 gene ( COL2A1 ). The identified variant showed impaired protein stability, and lead to dysfunction of type II collagen. In addition to pre and postnatal growth retardation, remarkable retardation of gross motor development and intellectual disability were noted. The latter was connected to cerebral malformations. The overall clinical phenotype of our current patient resembles spondyloepiphyseal dysplasia congenita (SEDC), but with extra phenotypic criteria. Conclusions The aim of this paper is twofold; firstly, raising awareness among orthopaedic surgeons when dealing with children manifesting multiple deformities, and secondly to broaden the clinical phenotype in patients with COL2A1 mutations of amino acid substitution (glycine to serine).