Fig. 3

Pedigree, sequencing peak map and location of the variation in gene and COL2A1 protein. The proband was indicated by an arrow. G504S-minus signs represented heterozygous COL2A1 variation carriers, double-minus signs, wild type. Slash filled symbols for males (squares) and females (circles) represented affected individuals with epiphyseal dysplasia, and spots, with sensorineural hearing loss. White filled symbols for squares and circles represented the normal family members (a). Sanger sequencing confirmed the co-segregation of the pathogenic COL2A1 variation with the phenotype in Family 1,908,322 (b). Structure of COL2A1 transcript 1 (NM_001844.5) with 54 exons. Pathogenic variation c.1510G>A was located in exon 23 and was marked with red and five previously reported spondyloepiphyseal dysplasia congenita (SEDC) accompanied causative variations associated with sensorineural hearing loss (SNHL) were distributed on several different exons (c). The triple-helical configuration of the type II procollagen was assembled from three α-1 chain encoded by COL2A1 and all of reported variations causing SEDC accompanied with SNHL are distributed within the triple-helical domain rather than C or N terminal propeptide (d). Reference website for drawing the structure diagram of the gene and procollagen: https://www.ncbi.nlm.nih.gov/