Trio whole-exome sequencing reveals a novel de novo mutation in COL2A1 gene in an Iranian patient with hypochondroplasia

Hypochondroplasia is a hereditary form of skeletal dysplasia characterized by very short stature, chest with short ribs, and disproportionately legs and arms. The COL2A1 gene encodes the alpha-1 chain of type II collagen and is the major structural part of the extracellular matrix. A variety of alterations in this gene have been shown to be responsible as the cause of skeletal dysplasia and cartilage defect. In this study, we performed a trio-analysis of whole-exome sequencing (WES) and in silico investigation for an Iranian patient with hypochondroplasia and her parents. The DNA samples were extracted from an 8 years old female patient and her parents. WES was conducted for these samples and the results were eventually confirmed and segregated via Sanger sequencing. Our findings demonstrated a novel de novo heterozygous missense variant in COL2A1 gene, chr12:48373338:C > T, NM_033150, c.G2482A, (P.G828R). By Sanger sequencing, this disease-causing variant was confirmed in the patient, while parents' Sanger results showed the presence of wild-type alleles of the gene as was introduced via WES. Additionally, computational databases predicted damaging effects for this mutation. Results of this study expand the variant frequency of COL2A1 gene and also exhibit foundational clues for genetic counselling and future hypochondroplasia diagnosis and therapy.