Abstract
OBJECTIVE: To investigate the clinical characteristics and prognostic significance of germline mutations in patients with myelodysplastic neoplasms（MDS）. METHODS: Clinical data from 407 patients with MDS［male, 252; female, 155; median age, 64（range, 19–85）years］diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The clinical features and prognostic effects of germline mutations were evaluated. RESULTS: The prevalence of germline mutations in patients with MDS was 5.9％（24/407）, peaking at 20.0％ in the group aged 21–30 years. The spectrum of germline mutations comprised DDX41（9 cases, 2.2％）, TP53（3 cases, 0.7％）, and single cases of RUNX1, TET2, MPL, CBL, ATRX, CEBPA, ETV6, IDH1, KDM5C, SBDS, GNAS, and CTC1. Patients with germline mutations exhibited significantly lower peripheral WBC counts than those without（1.87×10⁹/L vs 2.50×10⁹/L, P＝0.018）, but showed comparable median overall survival（21.3 months vs 21.1 months, P＝0.97）. Patients with DDX41 germline mutations, compared with those with other germline mutations, had a significantly older median age（65 vs 54 years, P＝0.010）, lower WBC counts（1.51×10⁹/L vs 2.31×10⁹/L, P＝0.040）, increased mean corpuscular volume（111.80 fl vs 97.25 fl, P＝0.003）, and a higher prevalence of normal karyotypes（100.0％ vs 53.3％, P＝0.022）. The most frequently co-occurring somatic mutations in DDX41 germline mutation carriers were ASXL1, TET2, and RUNX1. CONCLUSION: In this study, the detection rate of germline mutations in MDS patients was 5.9％（24/407）, peaking at 20％ in the group aged 21–30 years. DDX41 and TP53 were the most prevalent germline mutations. DDX41 mutation carriers displayed distinct clinical characteristics; however, germline mutations overall showed no significant prognostic effect.