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 - 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
SN - 2666-2477
VL - 3
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
IS - 2
M1 - 100094
ER -