Vazquez, MaribelChovanec, JackKim, JiwonDiMaggio, ThomasMilner, Joshua D.Francomano, Clair A.Gurnett, Christina A.Ritelli, MarcoColombi, MarinaLyons, Jonathan J.2023-05-182023-05-182022-02-22Vazquez M, Chovanec J, Kim J, et al. Hereditary alpha-tryptasemia modifies clinical phenotypes among individuals with congenital hypermobility disorders. HGG Adv. 2022;3(2):100094. Published 2022 Feb 22. doi:10.1016/j.xhgg.2022.100094https://hdl.handle.net/1805/33106Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding TPSAB1 copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalConnective tissueAlpha-tryptaseBasal serum tryptaseArticle