PMC8217077_01
Radiographs of the patients, patient III-10 (A-D, age 37) and patient II-5 (E-H, age 65). (A and E) Anteroposterior (AP) view of pelvis presented osteoarthritic changes including joint spaces narrowing, osteophytes formation and osteosclerosis in bilateral hip joints. Lateral view spine showed significant cervical spondylopathy (B and F) and degenerative changes in lumbar spine (C and G). Patient III-10 showed scoliosis in AP view of spine (D) while his father did not (H).
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Illustrative radiographs of the two patients (II-5 and III-10) are shown in Figure 1.
Pedigree of the affected Chinese family with early-onset osteoarthritis. Squares represent males and circles represent females. Black shapes represent affected family members, white shapes represent healthy members. The arrow indicates the proband (III-10). The shapes with a crossing line indicate that the person has already died.
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Besides the two patients, a total of 13 members in this family were also believed to be affected and 11 were clinically diagnosed with hip osteoarthritis and cervical spondylopathy (Figure 2).
Sequencing analysis of the partial COL2A1 gene. The heterozygous c.611C>G, p.Gly204Ala mutation in exon 9 of the COL2A1 gene was shown in the affected family members (B) but not in the normal family members (A). The mutation site is marked by a filled black square and the mutant codon (GGC to GCC) is circled by a blank black square.
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This heterozygous mutation co-segregated with osteoarthritis phenotype in all affected family members by Sanger sequencing (Figure 3).
Evolutionary conservation of the mutant amino acid residue of COL2A1. Multispecies alignment of COL2A1 orthologs shows that the mutant amino acid, p.G204A (marked by a black square), is conserved across species including Human, Gorilla, Chimpanzee, Cow, Chicken, Dog, Pig, Rat, Mouse, Xenopus, Zebrafish and Fugu. * indicates positions that have a single and fully conserved residue, : indicates conservation between groups of strongly similar properties, . indicates conservation between groups of weakly similar properties.
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Protein sequence alignment of COL2A1 in multiple species showed that the glycine at position 204 was highly conserved (Figure 4).