Genetic testing for the diagnosis and classification of joint hypermobility: a case report of 15 patients

Abstract Background Joint hypermobility (JH) is used to define the capability of a joint moving passively or actively beyond normal limits along physiological axes, which can be influenced by multiple factors (genetic factors, age, gender, weight and training), and the accurate incidence is unclear. In this study, we aimed to identify the genetic cause of JH in 15 patients from seven unrelated Chinese families. Results We identified seven pathogenic/likely-pathogenic variants: two novel mutations, in the COL6A2 and CHST14 genes, and five reported mutations in the COL11A1 , NALCN , GALNS and COL5A1 respectively. Based on the genetic testing, we were able to diagnose the precise condition for each patient: Stickler syndrome in Proband 1, the Ullrich congenital muscular dystrophy in proband 2, CLIFAHDD syndrome in proband 3, Mucopolysaccharidosis IVA in proband 4, Classical Ehlers-Danlos syndrome (EDS) in proband 5, and Musculocontractural EDS in proband 6. Moreover, this is the first time to describe the Musculocontractural EDS caused by CHST14 in China. Though the expression of the mRNA and protein have not significantly changed, we speculated that the mutation of the CHST14 may affect the sulfotransterase activity of the protein. Conclusions The diagnosis in all probands except proband 6 and 7 were corrected following genetic analysis, indicating the importance of the genetic testing in the diagnosis and classification of JH cases. Our findings also offered insight into the genotype-phenotypes relationship and expanded the mutation spectrum of the disease-causing genes in JH.