Estimation on risk of spontaneous abortions by genomic disorders from a meta‐analysis of microarray results on large case series of pregnancy losses

Abstract

A meta‐analysis on seven large case series (>1000 cases) of chromosome microarray analysis (CMA) on products of conceptions (POC) evaluated the diagnostic yields of genomic disorders and syndromic pathogenic copy number variants (pCNVs) from a collection of 35,130 POC cases. CMA detected chromosomal abnormalities and pCNVs in approximately 50% and 2.5% of cases, respectively. The genomic disorders and syndromic pCNVs accounted for 31% of the detected pCNVs, and their incidences in POC ranged from 1/750 to 1/12,000. The newborn incidences of these genomic disorders and syndromic pCNVs were estimated in a range of 1/4000 to 1/50,000 live births from population genetic studies and diagnostic yields of a large case series of 32,587 pediatric patients. The risk of spontaneous abortion (SAB) for DiGeorge syndrome (DGS), Wolf–Hirschhorn syndrome (WHS), and William–Beuren syndrome (WBS) was 42%, 33%, and 21%, respectively. The estimated overall risk of SAB for major genomic disorders and syndromic pCNVs was approximately 38%, which was significantly lower than the 94% overall risk of SAB for chromosomal abnormalities. Further classification on levels of risk of SAB to high (>75%), intermediate (51%–75%), and low (26%–50%) for known chromosomal abnormalities, genomic disorders, and syndromic pCNVs could provide evidence‐based interpretation in prenatal diagnosis and genetic counseling.

Genetic analysis of chorionic villus tissues in early missed abortions

“…We identified submicroscopic pCNVs in 2.2% (25/1160) of our cases, which is same to 2.2% by Wang et al 6 . Three recurrent pCNVs, including 22q11.2 microdeletion, 7q11.23 microdeletion, and 16p13.11 microduplication, were reported in previous studies on miscarriage 21,37,42,43 . The possible underlying mechanism that results in early embryonic death may be a malformed fetal cardiovascular system resulting from 22q11.2 deletion and 7q11.23 deletion 6 .…”

“…Until now, karyotyping, CMA, as well as CNV-seq were the main technologies for identifying chromosomal anomalies [19][20][21] . Karyotyping is considered the "gold standard" for cytogenetics, its advantage is that it can detect chromosomal numerical, and visible structural abnormalities.…”

A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD

“…Pathogenic CNVs are also known as recurrent and non-recurrent. While non-recurrent pathogenic CNVs occur sporadically in the genome, with probable origins in replication errors or DNA repair mechanisms, they cover different gene contents and consequently present variable phenotypes 55 – 57 . Recurrent pathogenic CNVs, in turn, are associated with known and characterized microdeletion and microduplication syndromes.…”

A Cohort Study of Individuals with Neurodevelopmental Disorders and/or Congenital Anomalies Investigated by High- Resolution Chromosomal Microarrays in Southern Brazil: The Significance of Autism Spectrum Disorder

“…Pathogenic CNVs are also known as recurrent and non-recurrent. While non-recurrent pathogenic CNVs occur sporadically in the genome, with probable origins in replication errors or DNA repair mechanisms, they cover different gene contents and consequently present variable phenotypes [52][53][54]. Recurrent pathogenic CNVs, in turn, are associated with known and characterized microdeletion and microduplication syndromes.…”