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

Fibrochondrogenesis 1, an autosomal recessive syndrome, is a rare disease that causes short‐limbed skeletal dysplasia. Mutations in the gene encoding the α1 chain of type XI collagen (COL11A1) are seen to be the main cause of this disease. We present an 18‐week Iranian male aborted fetus with Fibrochondrogenesis 1 from consanguineous parents. Whole‐exome sequencing 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. Bioinformatic 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.

Integrated Analysis of Transcriptome Expression Profiles Reveals miRNA-326–NKX3.2-Regulated Porcine Chondrocyte Differentiation

“…A large number of DEGs that play essential roles in the regulation of bone development were identified. Key candidate genes were further identified through a combination of functional analysis with literature mining, including NKX3.2 [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ], WLS [ 41 , 42 , 43 ], GREM1 [ 44 , 45 , 46 ], FGFR3 [ 47 , 48 , 49 , 50 , 51 ], HHEX [ 52 , 53 , 54 ], COL11A1 [ 55 , 56 , 57 ], and WNT16 [ 58 , 59 ]. These genes were mainly enriched in the BMP, FGF, Wnt, and Notch signaling pathways, suggesting that they are involved in the development of the pig vertebral column.…”

“…A novel deleterious heterozygous mutation in COL11A1 was associated with severe skeletal dysplasia [ 56 ]. A novel missense variant (G to A in exon 45) of COL11A1 resulted in short-limb skeletal dysplasia [ 57 ]. WTN16 , a ligand of the Wnt signaling pathway, is associated with bone density, cortical thickness, bone strength, and fracture risk [ 58 , 59 ].…”