High Prevalence of Connective Tissue Gene Variants in Professional Ballet

Abstract

Background: There is a high prevalence of hypermobility spectrum disorder (HSD) in dancers. While there is no known genetic variant for HSD, hypermobile Ehlers-Danlos syndrome is a genetic disorder that exists within HSD. There are many connective tissue disorders (CTDs) with known (and unknown) genes associated with hypermobility. Hypermobility has distinct advantages for participation in flexibility sports, including ballet. Purpose: To determine the prevalence of gene variants associated with hypermobility in a large professional ballet company. Study Design: Cross-sectional study; Level of evidence, 3. Methods: In this cross-sectional investigation, 51 professional male and female dancers from a large metropolitan ballet company were eligible and offered participation after an oral and written informed consent process. Whole blood was obtained from peripheral venipuncture, and DNA was isolated. Isolated DNA was subsequently enriched for the coding exons of 60 genes associated with CTD that included hypermobility as a phenotype, including Ehlers-Danlos syndromes, osteogenesis imperfecta, Marfan syndrome, and others. Genes were targeted with hybrid capture technology. Prepared DNA libraries were then sequenced with next-generation sequencing technology. Genetic database search tools (Human Gene Mutation Database and e!Ensembl, http://useast.ensembl.org/ ) were used to query specific variants. Descriptive statistics were calculated. Results: Of 51 dancers, 32 (63%) agreed to participate in DNA analysis (mean ± SD age, 24.3 ± 4.4 years; 18 men, 14 women). Twenty-eight dancers had at least 1 variant in the 60 genes tested, for an 88% prevalence. A total of 80 variants were found. A variant in 26 of the 60 genes was found in at least 1 dancer. Among the 28 dancers with variants, 16 were found in the TTN gene; 10 in ZNF469; 5 in RYR1; 4 in COL12A1; 3 in ABCC6 and COL6A2; 2 in ADAMTS2, CBS, COL1A2, COL6A3, SLC2A10, TNC, and TNXB; and 1 in ATP6V0A2, B4GALT7, BMP1, COL11A1, COL5A2, COL6A1, DSE, FBN1, FBN2, NOTCH1, PRDM5, SMAD3, and TGFBR1. Nine variants found in this population have never been reported. No identified variant was identical to any other variant. No identified variant was known to be disease causing. In the general population, the prevalence of each variant ranges from never reported to 0.33%. In the study population, the prevalence of each variant was 3.13%. There was no association between hypermobility scores and genetic variants. Conclusion: Genetic variants in CTD-associated genes are highly prevalent (88%) in professional ballet dancers. This may significantly account for the high degree of motion in this population.