Clinical Whole-Exome Sequencing Analysis Reveals a Novel Missense COL11A1 Mutation Resulting in an 18-Week Iranian Male Aborted Fetus with Fibrochondrogenesis 1: A Case Report

Abstract BackgroundFibrochondrogenesis 1, an autosomal recessive syndrome, is an infrequent and rare disease, causing short-limbed skeletal dysplasia. This syndrome is clinically characterized and distinguished by a small nose and anteverted bares, flat midface, shortened long bones, and a protuberant abdomen. Mutations in the gene encoding the α1 chain of type XI collagen (COL11A1) are seen to be the main cause of this disease.Case PresentationWe present an 18-week Iranian male aborted fetus with Fibrochondrogenesis 1 from consanguineous parents. Whole-exome sequencing (WES) revealed a novel missense variant from G to A in exon 45 of 68 in the COL11A1 gene (NM_080629.2: c.3440G>A, [p.G1147E, g.103404625]). The mutation was confirmed by Sanger sequencing and further, MutationTaster predicted this variant to be disease-causing.ConclusionBioinformatic analysis suggests that this variant is highly conserved in both nucleotide and protein levels, suggesting that it has an important function in the proper role of COL11A1 protein. In-silico analysis suggests that this mutation alters the COL11A1 protein structure through a Glycine to Glutamic acid substitution. This is a novel mutation and a rare variant as this variant is not reported in gmomAD, ExAC, or 1000 genome databases.To the best of the authors’ knowledge, this is the first study to report a novel pathogenic mutation in COL11A1 in association with Fibrochondrogenesis 1. Therefore, we suggest that WES can be used as a robust method to achieve rapid diagnosis and identification of pathogenic and novel mutations in patients.