Reproductive carrier screening among Chinese couples experiencing unexplained recurrent pregnancy loss

Area of Science:

• Genetics
• Reproductive Medicine
• Genomic Medicine

Background:

• Recurrent pregnancy loss (RPL) affects couples globally.
• Genetic factors are implicated in unexplained RPL.
• Carrier screening aids in identifying genetic risks for hereditary disorders.

Purpose of the Study:

• To determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in genes linked to autosomal recessive and X-linked disorders.
• To investigate these variants in Chinese couples experiencing unexplained RPL.
• To assess the clinical utility of carrier screening for reproductive counseling in this population.

Main Methods:

• Recruited 48 couples with unexplained RPL and 100 control couples.
• Utilized a carrier screening panel covering 485 genes for hereditary diseases.
• Performed genomic DNA sequencing and variant interpretation using ACMG guidelines.

Main Results:

• 93.8% of RPL couples carried at least one P/LP variant; 54.2% carried three or more.
• High carrier rates observed for GJB2, DUOX2, SRD5A2, ABCA4, and UGT1A1.
• SRD5A2 variant frequency was significantly higher in RPL females versus controls (P<0.05).
• Identified two couples at high risk for offspring with phenylketonuria or spinal muscular atrophy.

Conclusions:

• Unexplained RPL in Chinese couples shows a high prevalence of P/LP variants, especially in metabolic and developmental genes.
• These findings suggest genetic contributions to RPL.
• Carrier screening is clinically useful for reproductive genetic counseling.