# Prenatal Microarray Analysis of Pregnancies Without Ultrasound Anomalies: Establishment of Copy Number and Homozygosity Frequencies in Low-Risk Population

## TL;DR

This study analyzes prenatal microarray data from low-risk pregnancies to determine the frequency of genetic variations like copy number variants and homozygosity.

## Contribution

The study establishes baseline frequencies of pathogenic CNVs and homozygosity in a low-risk population without ultrasound or cfDNA abnormalities.

## Key findings

- Pathogenic CNVs occurred in ~1.26% of cases, with 52% linked to neurodevelopmental issues.
- Homozygosity was observed in ~1.32% of patients, mostly due to consanguinity.
- Variants of uncertain significance were found in 1.41%, with 90% being familial.

## Abstract

Objectives: The overall objective of this study is to examine prenatal patients ascertained without an abnormal ultrasound (US) or an abnormal cell-free DNA (cfDNA) finding to provide a unique understanding of pathogenic copy number variants, identity by descent (IBD) and variants of uncertain significance (VUSs) in a normal population. Methods: This study retrospectively provides an analysis of over 28,362 prenatal specimens ascertained without an abnormal US or abnormal cfDNA finding utilizing an SNP microarray. These specimens include at least 10 different ascertainment groups, including advanced maternal age (AMA), anxiety, abnormal maternal serum screen (MSS) with/without AMA, and a previous or familial child/pregnancy with a chromosome abnormality or a genetic disorder. Results: This study provides a basic understanding of pathogenic copy number variants (CNVs), homozygosity and VUSs in an essentially normal population. This low-risk population has a frequency of pathogenic CNVs of ~1.26%; however, ~52% were associated with neurodevelopmental microdeletions/microduplications and ~13% were associated with incidental findings. Overall, ~1.32% of these patients showed an increase in homozygosity, the majority due to consanguinity. Lastly, VUSs were seen in 1.41% of this group, of which ~90% were familial. Conclusions: Overall, these findings provide a better estimate of the baseline frequencies and types of pathogenic CNVs and homozygosity in a low-risk population. It provides insight into the distribution of stretches of homozygosity associated with identity by descent in this population and gives a better understanding of the extent of variants of uncertain significance in phenotypically unaffected individuals.