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.

Performance of Swedish Warmblood fragile foal syndrome carriers and breeding prospects

“…In humans, a LH1 activity of 52% was measured in carriers of a similar PLOD1 variant (c.2032G>A, p.Gly678Arg) as in the equine lethal WFFS allele, which is consistent with an intermediate phenotype, plausibly presenting a higher degree of joint laxity [ 33 ]. Likewise, a high prevalence of carriers of variants of connective tissue genes were found in professional ballet dancers, possibly accounting for the high degree of mobility in this population [ 34 ]. Interestingly, the walk seemed to be the most affected gait by WFFS carrier status, both from the traditional evaluating and linear descriptive evaluations in the NS and SJ subgroups.…”

TTN Variants Are Associated with Physical Performance and Provide Potential Markers for Sport-Related Phenotypes

“…Therefore, the TTN gene may be considered as a promising genetic marker for athletic status, which may underlie differences in the potential to achieve outstanding results in sports competition. However, analysis of the whole gene is demanding due to its complex structure and large size, and only a few studies have been undertaken to clarify its role in the formation of physical performance [ 20 , 25 , 31 ] and injury risk [ 26 ]. Recently, with DNA sequencing becoming widely available, it has been possible to determine the individual polymorphism located in the TTN gene that may influence elite athletic status, which was the main aim of our study.…”

“…Conversely, T allele carriers may be susceptible to injuries [ 20 , 33 ]. The importance of the TTN gene for muscle properties and injury risk was confirmed by Vera et al, who showed the association between connective tissue disorders (CTDs) and genetic variants within this gene [ 26 ]. In the future, knowledge of the TTN genotype in populations at higher injury risk, such as athletes and physically active people, may help to predict the consequences of physical activity and tailored training interventions specific to the TTN genotype [ 20 ].…”

“…Subsequent research has confirmed the key role of titin in the development of crucial skeletal and cardiac muscle functions, such as strength and stiffness, and highlighted its role in sports performance [ 6 , 20 , 25 , 26 ], and in all probability as argued by Perrin et al (2017) in the risk of injury [ 27 ]. The best-known variation within the TTN gene is the C>T polymorphism (rs10497520), which results in a lysine (Lys) transforming into a glutamic acid (Glu), which may affect the variability within the isoforms’ expression in muscle tissue [ 20 ].…”

Editorial Commentary: Personalized Hip Arthroscopy Outcome Prediction Using Machine Learning—The Future Is Here

“…The approach to management of certain complex conditions (e.g., cancer, heart disease, diabetes, and arthritis) is now significantly influenced not only by their phenotype, what we see during routine clinical evaluation, but also by their genotype. 1 That's right: People's genes, their genetic makeup, their DNA, who they aredthis information is being used not just for research but for clinical care. 2,3 Unfortunately, it is estimated that it takes 17 years for research evidence to reach clinical practice.…”