TY - JOUR
T1 - Hereditary alpha-tryptasemia modifies clinical phenotypes among individuals with congenital hypermobility disorders
AU - Vazquez, Maribel
AU - Chovanec, Jack
AU - Kim, Jiwon
AU - DiMaggio, Thomas
AU - Milner, Joshua D.
AU - Francomano, Clair A.
AU - Gurnett, Christina A.
AU - Ritelli, Marco
AU - Colombi, Marina
AU - Lyons, Jonathan J.
N1 - Funding Information:
This research was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH and by the National Institute of Arthritis and Musculoskeletal Disease (R01AR067715). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The authors declare no competing interests.
Funding Information:
This research was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases , NIH and by the National Institute of Arthritis and Musculoskeletal Disease ( R01AR067715 ). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
Publisher Copyright:
© 2022
PY - 2022/4/14
Y1 - 2022/4/14
N2 - 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.
AB - 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.
KW - EDS
KW - HSD
KW - HaT
KW - TPSAB1
KW - alpha-tryptase
KW - connective tissue
UR - http://www.scopus.com/inward/record.url?scp=85125859362&partnerID=8YFLogxK
U2 - 10.1016/j.xhgg.2022.100094
DO - 10.1016/j.xhgg.2022.100094
M3 - Article
C2 - 35287299
AN - SCOPUS:85125859362
VL - 3
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
SN - 2666-2477
IS - 2
M1 - 100094
ER -