Table 1.

Clinical features and gene-dose effects in hereditary α-tryptasemia syndrome

	Hereditary α-tryptasemia syndrome (α)		TPSAB1 duplication (αα)		TPSAB1 triplication (ααα)		P valuea
Serum tryptase, ng/ml Median Interquartile range	15.9 12.6–20.7		14.3 11.6–17.8		23.4 19.8–26.4		<0.0001
Manifestation	n	%	n	%	n	%	P valuea
Systemic venom reactionb	15/96	16	11/73	15	4/15	27	NS
Flushing/pruritus	49/96	51	33/73	45	12/15	80	0.022
IBS (Rome III)	34/70	49	26/53	49	7/12	58	NS
Chronic gastroesophageal reflux symptoms	62/96	65	42/73	49	15/15	100	0.001
Congenital skeletal abnormalityc	25/96	26	14/73	19	8/15	53	0.009
Retained primary dentition	20/96	21	12/73	16	7/15	47	0.016
Hypermobility (Beighton score ≥4)d	14/50	28	11/30	37	3/13	23	NS
COMPASS 31e	33/70	47	26/57	46	5/11	45	NS
Positive tilt-table test	11	≥11	6	≥8	4	≥26	ND
Arthralgia	43/96	45	31/73	42	11/15	73	0.045
Body pain/headache	45/96	47	32/73	44	11/15	73	0.049
Sleep disruption	37/96	39	23/73	32	11/15	73	0.004

IBS, irritable bowel syndrome; ND, not able to determine. Statistically significant differences are marked in bold. NS, not significant.

^aComparison of duplication (αα) and triplication (ααα) carriers at TPSAB1.

^bSystemic immediate hypersensitivity reaction consistent with IgE-mediated response to stinging insects, as described in the Supplementary Note.

^cPresence of a congenital skeletal malformation (the complete list of malformations identified is provided in the Supplementary Note) or diagnosis of EDS.

^dOnly individuals over 12 years of age and who could be directly visualized were assessed and reported.

^eNumber of individuals with a composite score above the upper 95% confidence interval of the median established in a healthy control cohort without increased copy number at TPSAB1.