Hereditary alpha-tryptasemia modifies clinical phenotypes among individuals with congenital hypermobility disorders
Maribel Vazquez,
Jack Chovanec,
Jiwon Kim,
Thomas DiMaggio,
Joshua D. Milner,
Clair A. Francomano,
Christina A. Gurnett,
Marco Ritelli,
Marina Colombi,
Jonathan J. Lyons
Affiliations
Maribel Vazquez
Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD 20892, USA
Jack Chovanec
Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD 20892, USA
Jiwon Kim
Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD 20892, USA
Thomas DiMaggio
Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD 20892, USA
Joshua D. Milner
Division of Allergy, Immunology, and Rheumatology, Columbia University, New York, NY 10027, USA
Clair A. Francomano
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Christina A. Gurnett
Washington University of St. Louis, St. Louis, MO 63103, USA
Marco Ritelli
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy
Marina Colombi
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy
Jonathan J. Lyons
Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD 20892, USA; Corresponding author
Hereditary 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.
