Spectrum and carrier frequency of DMD in Yueyang, China: a population-based analysis using NGS and MLPA

Background Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the DMD gene. Understanding the carrier frequency and mutation spectrum in specific populations is critical for genetic counseling and early intervention. However, data on DMD carrier frequency among women of childbearing age and early pregnancy in Yueyang City, China, remain limited. This study aimed to characterize the carrier rate and mutation profile to support preventive strategies and reduce disease incidence. Methods A total of 25,611 women of childbearing age or early pregnancy from Yueyang City were enrolled. Combined next-generation sequencing and multiplex ligation-dependent probe amplification were used to detect pathogenic/likely pathogenic (P/LP) variants, copy number variants (CNVs), and small indels. Variants were classified per established guidelines. Carrier rates and geographical distribution were analyzed. Prenatal diagnosis was offered to identified carriers with follow-up to assess outcomes. Results Twenty-eight women were identified as P/LP carriers (0.11%), representing 25 distinct variants. CNVs constituted the majority (71.43%), with exon 45–55 deletions (64.29%) predominating over duplications (7.14%); notably, 13/18 CNVs clustered in this hotspot. SNVs and small indels accounted for the remaining 28.57%. Intra-regional variation was marked, with the highest rate in Yunxi District (0.74%). Additionally, 81 VUSs (51 distinct types) were detected, 66.67% being missense. One male fetus inheriting a maternal VUS developed DMD-like features postpartum. Overall, 12 variants (1 LP, 11 VUSs) were previously unreported, including a nonsense variant c.3502G>T (p.E1168*) classified as LP. Conclusion This first population-based study in Yueyang City, China, characterized the DMD carrier frequency (0.11%) and mutation spectrum among women of childbearing age or in early pregnancy. It revealed geographical heterogeneity and a high prevalence of CNVs, especially exon 45–55 deletions. Crucially, it highlights the underappreciated screening value of VUS. We recommend focused attention on VUS, particularly those with Bayesian scores ≥3, in genetic counseling and prenatal diagnosis to improve preventive strategies and reduce DMD incidence.