Purpose: To identify potential disease-causing mutation in the COL2A1 gene in a Chinese family with autosomal dominant spondyloepiphyseal dysplasia congenita (SEDC) and to analyze the phenotype-genotype correlation.
Methods: Complete physical and radiographic examinations of four affected individuals from SEDC family were conducted. Genomic DNA were isolated from peripheral blood leukocytes. All 54 exons and exon-intron boundaries of the COL2A1 gene were amplified by polymerase chain reaction (PCR) and bidirectionally sequenced.
Results: All four affected individuals were found carried a novel missense mutation of c.2224G>A (p.Gly687Ser) in COL2A1, while normal members of the family and 50 healthy controls did not have this mutation. Protein prediction of missense mutation by polyphen-2 and SIFT software and mutation taster indicated severe damage to the function.
Conclusions: c.2224G>A (p.Gly687Ser) is a novel mutation of COL2A1 associated with spondyloepiphyseal dysplasia congenital. There are heterozygous of phenotype for the mutation in members of the pedigree analyzed. Onset becomes more earlier and severe with each successive generation.