2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Whole-exome sequencing on product of conception: A cohort study to evaluate clinical utility and genetic etiology for pregnancy loss

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This cohort study aimed to evaluate the clinical utility and genetic etiology of pregnancy loss through whole-exome sequencing (WES) on products of conception (POCs). The study analyzed a cohort of 102 cases with normal karyotype and absence of pathogenic copy-number variants (pCNVs).<br /><br />The overall abnormality detection rate (ADR) in this cohort was found to be 21% for pathogenic and likely pathogenic variants, with an additional 14% for variants of uncertain significance favoring pathogenicity (VUSfp). Combined with cytogenetic analysis, the ADR for chromosomal abnormalities/pCNVs was 54% for POC specimens.<br /><br />The study identified recurring associations between genes and fetal death, with 42% of the genes in 47% of the cases showing such associations. The most prevalent disease categories among cases with pathogenic and likely pathogenic variants were multi-system disorders, cardiac anomalies, neurodevelopmental disorders, and skeletal dysplasia.<br /><br />The study also assessed the clinical utility of WES by evaluating the ADR in different maternal age groups and trimesters of pregnancy. It found that the ADR was higher in pregnant women aged 35 years or older and in the second trimester.<br /><br />Limitations of the study included the lack of parental study, CNV analysis, and assessment of high impact variants in non-OMIM genes. The authors suggested that further studies incorporating trio-analysis and CNV analysis would improve diagnostic yield and variant interpretation.<br /><br />In conclusion, this study demonstrated the clinical utility of WES in identifying genetic causes of pregnancy loss. It provided insights into the genetic etiology of fetal death and highlighted the importance of considering genes associated with adult-onset diseases or not previously recognized to play a role in early development.

Asset Subtitle

Presenting Author - Chen Zhao, PhD, DABMGG, FACMG; Co-Author - Hongyan Chai, PhD; Co-Author - Hui Zhang, MD, PhD; Co-Author - Yong-hui Jiang, MD, PhD; Co-Author - Peining Li, PhD; Co-Author - Allen E. Bale, MD;

Meta Tag

Exome sequencing

Genetic Diversity

Genetic Testing

Identification of Disease Genes

NextGen Sequencing

Pathogenesis

Prenatal Diagnosis

Co-Author Hongyan Chai, PhD

Co-Author Hui Zhang, MD, PhD

Co-Author Yong-hui Jiang, MD, PhD

Co-Author Peining Li, PhD

Co-Author Allen E. Bale, MD

Presenting Author Chen Zhao, PhD, DABMGG, FACMG

Keywords

cohort study

clinical utility

genetic etiology

pregnancy loss

whole-exome sequencing

abnormality detection rate

chromosomal abnormalities

recurring associations

maternal age groups

fetal death