Table 1_The genetic landscape of congenital neutropenia in Poland: summary of the nationwide screening campaign.xlsx

This work summarizes 15 years of genetic research on neutropenia in the Polish pediatric cohort, explores the distribution and spectrum of disease-causing genetic variants associated with congenital neutropenia in Poland, and demonstrates the impact of a nationwide information campaign on increasing the efficiency of patient recruitment. The study included 126 patients with suspected congenital neutropenia recruited in 2008–2019 and 291 patients recruited in 2020–2023 as part of the FixNet project, which featured a nationwide information campaign. Molecular analyses were performed using Sanger sequencing (91 patients) and targeted next-generation sequencing (NGS) (326 patients) in a panel of neutropenia-related genes. The information campaign significantly increased the number of referred patients from 10.5 per year to 72.75 per year. Based on the results obtained, 102 patients belonging to 80 different families were diagnosed with severe congenital neutropenia (SCN) and neutropenia-related syndromes, the majority (43%) of whom harbored variants in the ELANE gene, including 12 novel ones. Most of the remaining cases were SBDS, CLPB, SRP54, and CXCR4 gene defects. This work describes the largest cohort of genetic variations associated with suspected congenital neutropenia (CN) in Poland and is an important contribution to the international SCN registry.

本研究总结了针对波兰儿科队列的15年中性粒细胞减少症遗传学研究成果，系统探明了波兰境内与先天性中性粒细胞减少症（congenital neutropenia, CN）相关的致病遗传变异的分布特征与变异谱系，并证实了全国性信息宣传活动对提升患者招募效率的积极作用。
本研究纳入2008-2019年招募的126例疑似先天性中性粒细胞减少症患者，以及2020-2023年依托FixNet项目（该项目开展了全国性信息宣传活动）招募的291例患者。分子分析环节分别采用桑格测序（Sanger sequencing）对91例患者样本进行检测，采用靶向下一代测序（next-generation sequencing, NGS）针对中性粒细胞减少症相关基因组合对326例患者样本开展检测。
该信息宣传活动显著将转诊患者的年招募量从10.5例提升至72.75例。基于本次研究结果，来自80个不同家系的102例患者被确诊为重型先天性中性粒细胞减少症（severe congenital neutropenia, SCN）及中性粒细胞减少症相关综合征；其中43%的患者携带ELANE基因变异，包括12种新发致病变异。其余多数病例为SBDS、CLPB、SRP54及CXCR4基因缺陷。
本研究描述了波兰境内规模最大的疑似先天性中性粒细胞减少症相关遗传变异队列，是对国际SCN注册库的重要学术贡献。