[Genetic aetiology of spontaneous abortion detected by exome sequencing]

Objective: To explore the potential pathogenic genes and variants of spontaneous abortion by exome sequencing (ES). Methods: From September to December 2024, 20 spontaneous abortion samples with no chromosomal abnormalities detected by chromosomal microarray analysis (CMA) in the Women's Hospital of Nanjing Medical University were selected for familial ES detection. According to the American College of Medical Genetics and Genomics (ACMG) guidelines (2015 edition), the pathogenicity of the sequencing results was interpreted, and the possible pathogenic or pathogenic gene variants were verified by Sanger sequencing. Results: Of the 20 patients with spontaneous abortion, 2 were found to have genetic variants that might be related to spontaneous abortion: KYNU gene c.766G>T(p.Gly256Ter) and c.235C>T(p.Gln79Ter) compound heterozygous variants, which were likely pathogenic (paternal) and pathogenic (maternal), respectively, and were associated with xanthurenic aciduria and vertebral-heart, kidney, limb deficiency syndrome type 2 (VCRL2). DNM1L gene c.185C>T(p.Pro62Leu), a likely pathogenic variant, was a de novo variant, which was associated with mitochondrial and peroxisome fission-deficient encephalopathy. Conclusions: ES technology could facilitate the genetic diagnosis of spontaneous abortion, and provide theoretical basis and guidance for subsequent genetic counseling and subsequent pregnancies.