AI Article Synopsis

  • Congenital malformations of the female genital tract (CM-FGT) involve abnormal development of reproductive organs and can also affect other systems, with no identified genetic causes until now.
  • A comprehensive whole-genome sequencing study was conducted on 590 participants in China, discovering various genetic anomalies associated with CM-FGT, including novel variants and highlighting ASH1L as a key pathogenic gene.
  • The study's findings enhance the understanding of the genetic factors contributing to CM-FGT and suggest potential for prenatal screening based on the identified spatiotemporal gene expression patterns during early uterine development.

Article Abstract

Background: Congenital malformations of the female genital tract (CM-FGT) are characterized by abnormal development of the fallopian tubes, uterus, and vagina, often accompanied by malformations in the urinary system, bones and hearing. However, no definitive pathogenic genes and molecular genetic causes have been identified.

Methods: We present the largest whole-genome sequencing study of CM-FGT to date, analyzing 590 individuals in China: 95 patients, 442 case-controls, and 53 familial controls.

Results: Among the patients, 5.3% carried known CM-FGT-related variants. Pedigree and case-control analyses in two dimensions of coding and non-coding regulatory regions revealed seven novel de novo copy number variations, 12 rare single-nucleotide variations, and 10 rare 3' untranslated region (UTR) mutations in genes related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. Single-cell sequencing data showed that the majority of CM-FGT-related risk genes are spatiotemporally specifically expressed early in uterus development.

Conclusions: In conclusion, this study identified novel variants related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. The findings provide insights into the genetic variants underlying CM-FGT, with single-cell sequencing data revealing spatiotemporal specific expression patterns of key risk genes early in uterine development. This study significantly advances the understanding of CM-FGT etiology and genetic landscape, offering new opportunities for prenatal screening.

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Source
http://dx.doi.org/10.1007/s12519-024-00839-6DOI Listing

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