Incidence of the 22q11.2 deletion in a large cohort of miscarriage samples

Abstract

BackgroundThe 22q11.2 deletion syndrome is the most common microdeletion syndrome in livebirths, but data regarding its incidence in other populations is limited and also include ascertainment bias. This study was designed to determine the incidence of the 22q11.2 deletion in miscarriage samples sent for clinical molecular cytogenetic testing.ResultsTwenty-six thousand one hundred one fresh product of conception (POC) samples were sent to a CLIA- certified, CAP-accredited laboratory from April 2010–-May 2016 for molecular cytogenetic miscarriage testing using a single-nucleotide polymorphism (SNP)-based microarray platform. A retrospective review determined the incidence of the 22q11.2 deletion in this sample set. Fetal results were obtained in 22,451 (86%) cases, of which, 15 (0.07%) had a microdeletion in the 22q11.2 region (incidence, 1/1497). Of those, 12 (80%) cases were found in samples that were normal at the resolution of traditional karyotyping (i.e., had no chromosome abnormalities above 10 Mb in size) and three (20%) cases had additional findings (Trisomy 15, Trisomy 16, XXY). Ten (67%) cases with a 22q11.2 deletion had the common ~3 Mb deletion; the remaining 5 cases had deletions ranging in size from 0.65 to 1.5 Mb. A majority (12/15) of cases had a deletion on the maternally inherited chromosome. No significant relationship between maternal age and presence of a fetal 22q11.2 deletion was observed.ConclusionsThe observed incidence of 1/1497 for the 22q11.2 deletion in miscarriage samples is higher than the reported general population prevalence (1/4000–1/6000). Further research is needed to determine whether the 22q11.2 deletion is a causal factor for miscarriage.

The Belgian MicroArray Prenatal (BEMAPRE) database: A systematic nationwide repository of fetal genomic aberrations

“…Second, prenatal cases with ultrasound anomalies are more likely to be terminated. Finally, 22q11.2 pregnancies are thought to be more prone to end in a miscarriage: in a recent study in which the incidence of 22q11.2 deletions in 26 101 products of conception was examined, 21 12/9398 (0.13%) samples that were normal at karyotype resolution had an isolated 22q11.2 deletion, approaching the prevalence in our prenatal population. Of our 41 cases, 53.7% had an ultrasound anomaly that was clearly related to the genetic finding.…”

Noninvasive screening by cell‐free DNA for 22q11.2 deletion: Benefits, limitations, and challenges

“…The prevalence is similar in miscarriages and products of conception . This differs from the prevalence in an unselected cohort of neonates, which was found to be 1/3672 in a retrospective analysis of dried newborn bloodspots using microarray technology (CVS/AF vs neonates: OR 4.4821, 95% CI, 1.7370‐11.5655; POCs vs neonates: OR 3.6356, 95% CI, 1.5370‐8.5994)…”

Detection of cytogenomic abnormalities by OncoScan microarray assay for products of conception from formalin-fixed paraffin-embedded and fresh fetal tissues

“…OMA detected three pCNV of a deletion at 22q11.2, a deletion at 18q23, and a deletion at Xp22.33p22.31. A study of 22,451 miscarriage samples reported a higher incidence of 22q11.2 deletion in the miscarriages than the reported prevalence in the general population, indicating that the 22q11.2 deletion could be a causal factor for miscarriage [ 17 ]. Deletions of the distal region of 18q are associated with chromosome 18q deletion syndrome with wide phenotypic variability [ 18 ].…”