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

HGG Advances (Apr 2022)

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

Journal volume & issue: Vol. 3, no. 2
p. 100094

Abstract

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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.

Published in HGG Advances

ISSN: 2666-2477 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Biology (General): Genetics
Website: https://www.cell.com/hgg-advances/home

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