Prevalence and impact of the KIT M541L variant in patients with mastocytosis

Activating mutations in , particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous M541L has been primarily reported in patients with pediatric mastocytosis. We thus examined the prevalence of this variant in pediatric and adult patients with mastocytosis ( = 100) compared to ancestry-matched 1000 genomes controls ( = 500) and patients with idiopathic anaphylaxis ( = 23). We then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the M541L variant. Overall, the M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort ( = 13/81) without M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. This study uniquely examines the prevalence and impact of the M541L variant in both adult and pediatric patients with mastocytosis further stratified by disease variant. To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the M541L locus.