Abstract
Objective: Fetal nuchal translucency (NT) is assessed by ultrasound as a screening tool
for aneuploidy at 11-13+6 weeks’ gestation. Fetuses with increased NT but apparently
normal karyotyping result are still at higher risk of structural abnormality and a range of
genetic syndromes, which may be related to major and submicroscopic chromosomal
abnormalities. The aim of our study is to report the prevalence of submicroscopic
chromosomal abnormalities in a cohort of apparently euploid fetuses that presented with
increased NT.
Methods: DNA was extracted from stored CVS specimens relating to fetuses found to
have increased NT >3.5mm during first trimester screening. These samples were
examined by microarray based comparative genomic hybridization (aCGH) using a 44K
oligonucleotide array specifically constructed for prenatal screening. Variations in copy
number (CNVs) were reported after excluding known non-pathogenic variants and after
validation with multiplex ligation-dependent probe amplification (MLPA) or Real-Time
Quantitative PCR (RT-qPCR). The prevalence of pathogenic CNVs is reported and the
association with NT and other ultrasound findings described.
Results: CNVs were reported in 6/48 (12.5%) cases by aCGH and the microdeletions or
microduplications ranging from 1.07Mb to 7.80Mb. Five of these were validated by
MLPA/RT-qPCR and four (9.5%) were considered to be pathogenic and clinical
significant. The incidence of pathogenic CNV was 20% (2/10) among those cases with
other sonographic anomalies, and 5.3% (2/38) among those without.
Conclusions: aCGH allows detection of submicroscopic chromosomal abnormalities of
which the prevalence may be increased in fetuses with NT>3.5mm and an apparently
normal karyotype.
for aneuploidy at 11-13+6 weeks’ gestation. Fetuses with increased NT but apparently
normal karyotyping result are still at higher risk of structural abnormality and a range of
genetic syndromes, which may be related to major and submicroscopic chromosomal
abnormalities. The aim of our study is to report the prevalence of submicroscopic
chromosomal abnormalities in a cohort of apparently euploid fetuses that presented with
increased NT.
Methods: DNA was extracted from stored CVS specimens relating to fetuses found to
have increased NT >3.5mm during first trimester screening. These samples were
examined by microarray based comparative genomic hybridization (aCGH) using a 44K
oligonucleotide array specifically constructed for prenatal screening. Variations in copy
number (CNVs) were reported after excluding known non-pathogenic variants and after
validation with multiplex ligation-dependent probe amplification (MLPA) or Real-Time
Quantitative PCR (RT-qPCR). The prevalence of pathogenic CNVs is reported and the
association with NT and other ultrasound findings described.
Results: CNVs were reported in 6/48 (12.5%) cases by aCGH and the microdeletions or
microduplications ranging from 1.07Mb to 7.80Mb. Five of these were validated by
MLPA/RT-qPCR and four (9.5%) were considered to be pathogenic and clinical
significant. The incidence of pathogenic CNV was 20% (2/10) among those cases with
other sonographic anomalies, and 5.3% (2/38) among those without.
Conclusions: aCGH allows detection of submicroscopic chromosomal abnormalities of
which the prevalence may be increased in fetuses with NT>3.5mm and an apparently
normal karyotype.
| Bidragets oversatte titel | Identifikation af submikroskopiske kromosomale aberrationer i fostre med øget nakkefold og tilsyneladende normal karyotype: aCGH ved øget nakkefold |
|---|---|
| Originalsprog | Engelsk |
| Tidsskrift | Ultrasound in Obstetrics & Gynecology |
| Vol/bind | 38 |
| Udgave nummer | 3 |
| Sider (fra-til) | 314-9 |
| Antal sider | 6 |
| ISSN | 0960-7692 |
| DOI | |
| Status | Udgivet - sep. 2011 |
| Udgivet eksternt | Ja |