Although increased levels of basal serum tryptase (BST) may indicate a diagnosis of systemic mastocytosis (SM), high elevations can still be tolerated in people with hereditary α-tryptasemia, according to an article published in Blood Advances.

To examine the overall utility of tryptase genotyping, the researchers cloned, long-read sequenced, and assembled the human tryptase locus containing a TPSAB1 replication. They also validated their findings in vitro and in silico.

They discovered an increased TPSAB1 copy number at the tryptase locus, which has been found to encode canonical α-tryptase protein.

Furthermore, the TPSAB1 replications encoding distinguished duplicated α-tryptase have been associated with the presence of an expanded promoter. A distinctive haplotype that preserves the identified overactive promoter at replicated TPSAB1 loci has also been identified. Moreover, the increased basal values of distinguished duplicated α-tryptase appear to be linked with the increased activity of the basal promoter.

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The expression of distinguished duplicated α-tryptase transcripts are found to be extremely high in public data sets. However, when BST levels were modeled according to the TPSAB1 replication number, the clinical reference ranges could be entirely redefined.

“To our knowledge, the application of genotypic information to determine clinical reference ranges in a personalized manner has not previously been used in laboratory medicine. However, many common clinical laboratory measurements (eg, immunoglobulin levels) are not normally distributed, and in some cases, outliers may be similarly determined by heritable traits,” Chovanec and colleagues wrote.

“Thus, we anticipate this kind of precision approach to clinical laboratory medicine will expand in the future as next-generation sequencing becomes increasingly utilized in standard clinical practice.”

Serum tryptase is a common biomarker used in the diagnostics of myeloid neoplasms, while BST levels higher than 20 ng/mL are a minor criterion for the diagnosis of SM.


Chovanec J, Tunc I, Hughes J, et al. Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasmsBlood Adv. Published online May 9, 2023. doi:10.1182/bloodadvances.2022007936