To explore the pathogenicity of partial duplication of dystrophin gene (called DMD gene) in pregnant women found by carrier screening.

From March to November 2022, two pregnant women (pregnant woman 1, 2) who carried partial duplication in the DMD gene found by carrier screening at Department of Prenatal Diagnosis, Nanjing Women and Children′s Healthcare Hospital were enrolled. Carriers were screened by capillary electrophoresis. Partial duplications in DMD gene were confirmed by multiplex ligation-dependent probe amplification (MLPA). The copy number variation (CNV) of DMD gene was detected by MLPA in 2 pregnant women′s family members, and a pedigree chart of the families carrying a partial duplication in DMD gene was drawn. Pathogenicity of gene mutation was classified according to Standards and Guidelines for the Interpretation of Sequence Variants set by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ＂ACMG guidelines＂). The pathogenicity of the partial duplication in DMD gene was interpreted based on database records and their reported literature and clinical manifestations of males carrying the duplication. This study was reviewed and approved by the Ethics Committee of Nanjing Women and Children′s Healthcare Hospital [Approval No. (2020)KY-057)], and all participants signed written consent forms.

①Carrier screening identified that pregnant woman 1, 2 carried duplications of exon 1-6 and exon 1-9 in DMD gene, respectively, corresponding to ChrX: 33339448-32816399 (GRCh38) and ChrX: 33339448-32697885 (GRCh38). ② Duplication of exon 1-6 in DMD gene carried by pregnant woman 1 have been documented in databases and its pathogenicity was reported in related literature; however, duplication of exon 1-9 in DMD gene carried by pregnant woman 2 has not been recorded or reported. ③ Pedigree analysis showed that there were healthy males in two pregnant women′s family carrying the same duplications, suggesting those two duplications are likely to be non-pathogenic.

To provide accurate genetic counselling and avoid unnecessary invasive prenatal diagnosis measure, pedigree analysis of DMD gene duplications should be considered when carrier screening identified variants with variants of uncertain significance (VUS) in DMD gene.