Maladaptive Neuroplasticity in Corticospinal Tract after Ankle Sprain: Causal Links Established by Mendelian Randomization.

PURPOSE: It has been hypothesized that the corticospinal tract (CST) is involved in the neural origins underlying muscular deficits after an ankle sprain. Microstructural differences in the CST have been reported in patients with and without a history of ankle sprain, but the causal links between the CST and the injuries have not been verified. This study aimed to explore whether genetically predisposed ankle sprains would impair the integrity and organization of CST neurites, manifesting as reduced fractional anisotropy (FA) and increased orientation dispersion index (ODI). METHODS: Single-nucleotide polymorphisms (SNP) associated with ankle sprains were identified from genome-wide association studies (GWAS) in FinnGen based on hospital discharge records (7223 cases and 245,598 controls). Outcome statistics for CST microstructures were collected from the GWAS from diffusion-weighted-imaging outcomes in the UK Biobank (33,224 participants). Random-effect, inverse-variance weighted Mendelian randomization was used as the primary method. RESULTS: Eighteen SNP were selected as forming possible causal links between ankle sprains and CST structure; F value ranged from 755 to 1026. Ankle sprains were associated with a reduction in the FA of the right CST ( ß = -0.033, P = 0.0439), whereas no significant effects were observed on the left side ( ß = -0.029, 0.004; P = 0.0748). Ankle sprains significantly increased the ODI of the left CST ( ß = 0.053, P = 0.0036) and the right CST ( ß = 0.038, P = 0.0259). No significant pleiotropy or heterogeneity was observed in the analyses. CONCLUSIONS: A genetic predisposition to ankle sprains can lead to maladaptive neuroplasticity of the CST, manifesting as abnormally organized neurites.

Two genetic loci associated with ankle injury.

Ankle injuries, including sprains, strains and other joint derangements and instability, are common, especially for athletes involved in indoor court or jumping sports. Identifying genetic loci associated with these ankle injuries could shed light on their etiologies. A genome-wide association screen was performed using publicly available data from the Research Program in Genes, Environment and Health (RPGEH) including 1,694 cases of ankle injury and 97,646 controls. An indel (chr21:47156779:D) that lies close to a collagen gene, COL18A1, showed an association with ankle injury at genome-wide significance (p = 3.8x10-8; OR = 1.99; 95% CI = 1.75-2.23). A second DNA variant (rs13286037 on chromosome 9) that lies within an intron of the transcription factor gene NFIB showed an association that was nearly genome-wide significant (p = 5.1x10-8; OR = 1.63; 95% CI = 1.46-1.80). The ACTN3 R577X mutation was previously reported to show an association with acute ankle sprains, but did not show an association in this cohort. This study is the first genome-wide screen for ankle injury that yields insights regarding the genetic etiology of ankle injuries and provides DNA markers with the potential to inform athletes about their genetic risk for ankle injury.

Genetic association between ACTN3 polymorphism and risk of non-acute ankle sprain.

In this study, we investigated the association between ACTN3 R577X polymorphism and non-acute ankle sprain by measuring the allele frequency and genotype distribution of ACTN3 in a Chinese Han population. We recruited 100 patients with non-acute ankle sprain and 100 healthy controls with no history of ankle injuries. Mass spectrometric analysis of single nucleotide polymorphism was used to analyze the genotype and allele frequencies of ACTN3. Results showed that the genotype frequency of RR in patients was 12.0%, which was significantly lower than that of the controls (24.0%) (OR = 1.7; 95%CI = 1.5-2.7; P = 0.001). The frequency distribution of the R allele in patients and controls were 68.5 and 56.7%, respectively (P = 0.002). Moreover, frequency of the RR genotype exhibited a downward linear trend with increased incidences of ankle sprain. Our results suggest that ACTN3 R577X polymorphism is associated with non-acute ankle sprain in the Chinese Han population.

The association between the ACTN3 R577X polymorphism and noncontact acute ankle sprains.

Ankle sprains are one of the most severe musculoskeletal soft tissue injuries during physical activity. Although many risk factors have been offered, it is unclear why some individuals develop noncontact ankle sprains when participating in comparable levels of physical exertion under identical environmental conditions and others do not. The ACTN3 gene that encodes the α-actinin-3 protein, which is, only expressed in the Z line of fast glycolytic muscle fibres was found to associate with power/strength performance. The aim of this study was therefore to investigate whether the ACTN3 gene polymorphism is associated with noncontact acute ankle sprains. One hundred and forty-two participants with clinically diagnosed noncontact acute ankle sprains as well as 280 physically active controls participants without any history of ankle sprains were included in this case-control genetic association study. The RR genotype (odds ratio (OR) = 0.56; 95% confidence interval (CI), 0.32-0.65, P = 0.011) and R allele (OR = 0.64; 95% CI, 0.37-0.68, P = 0.002) of the ACTN3 were significantly low-represented in the acute ankle sprains group compared with the control group. The ACTN3 R577X is associated with acute ankle sprains in Chinese participants in this study. This is the first study to suggest that an individual with a RR genotype is at a decreased risk of acute ankle sprains.

[Osteogenesis imperfecta Type 1: a case presentation with a new mutation in gene COL1A1]. / Osteogenesis imperfecta Typ 1: Fallbericht mit bis dato nicht beschriebener Mutation im COL1A1-Gen.

In a 4 year old girl the diagnosis osteogenesis imperfecta type I was suspected by following clinical criteria: four fractures after small trauma, intensive blue sclera, anomalies of dental enamel, macrocephalie with frontal bassing. Clinical diagnosis could be verified by moleculargenetic analysis, a newly recognized heterozygous point mutation (Arg420Stop) in the COL1A1-gene was found.