Frequency of de novo PRSS1 pathogenic variants in a French cohort of idiopathic pancreatitis

We read with great interest the recent publication by Lou et al ,1 which addressed the challenge of false positives in next-generation sequencing (NGS) due to highly homologous PRSS1 paralogs.2 3 PRSS1 was the first gene linked to chronic pancreatitis,4 with p.Arg122His (c.365G>A) and p.Asn29Ile (c.86A>T) being the most common mutations associated with the Mendelian form of the disease. Accurate identification of PRSS1 variants is crucial for genetic diagnosis and counselling, guiding both patient management and familial risk assessment. Although PRSS1 pathogenic variants are typically inherited in an autosomal dominant manner, they have also been reported in idiopathic pancreatitis, defined by the absence of precipitating factors and a negative family history prior to genetic analysis.5–8 However, large-scale data on the frequency of de novo PRSS1 variants in idiopathic pancreatitis remain limited. To address this gap, we analysed data from a large French cohort. From 1996 to July 2024, we genetically analysed 6872 patients with idiopathic pancreatitis, including both acute and chronic forms. Of these, 82 patients (1.2%) were identified to carry a PRSS1 pathogenic variant, with classifications based on the expert perspective of the Franco-Chinese GREPAN study group.9 …