OBJECTIVE: Fetal nuchal translucency (NT) is assessed by ultrasonography as a screening tool for aneuploidy at 11 to 13 + 6 weeks' gestation. Fetuses with increased NT but apparently normal karyotype 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 this study was 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 chorionic villus samples from fetuses found to have increased NT (> 3.5 mm) 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 polymerase chain reaction (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 ranged from 1.1 to 7.9 Mb. Five of these were validated by MLPA/real-time qPCR and four (8.3%) were considered to be pathogenic and clinically significant. The incidence of pathogenic CNVs was 20.0% (2/10) among those cases with other sonographic anomalies and 5.3% (2/38) among those without. CONCLUSION: aCGH allows detection of submicroscopic chromosomal abnormalities, the prevalence of which may be increased in fetuses with NT > 3.5 mm and an apparently normal karyotype.
OBJECTIVE: Fetal nuchal translucency (NT) is assessed by ultrasonography as a screening tool for aneuploidy at 11 to 13 + 6 weeks' gestation. Fetuses with increased NT but apparently normal karyotype 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 this study was 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 chorionic villus samples from fetuses found to have increased NT (> 3.5 mm) 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 polymerase chain reaction (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 ranged from 1.1 to 7.9 Mb. Five of these were validated by MLPA/real-time qPCR and four (8.3%) were considered to be pathogenic and clinically significant. The incidence of pathogenic CNVs was 20.0% (2/10) among those cases with other sonographic anomalies and 5.3% (2/38) among those without. CONCLUSION: aCGH allows detection of submicroscopic chromosomal abnormalities, the prevalence of which may be increased in fetuses with NT > 3.5 mm and an apparently normal karyotype.
Authors: Antina de Jong; Wybo J Dondorp; Merryn V E Macville; Christine E M de Die-Smulders; Jan M M van Lith; Guido M W R de Wert Journal: Hum Genet Date: 2014-02 Impact factor: 4.132
Authors: Malgorzata I Srebniak; Karin E M Diderich; Lutgarde C P Govaerts; Marieke Joosten; Sam Riedijk; Robert Jan H Galjaard; Diane Van Opstal Journal: Eur J Hum Genet Date: 2013-11-06 Impact factor: 4.246
Authors: Ye Cao; Zhihua Li; Jill A Rosenfeld; Amber N Pursley; Ankita Patel; Jin Huang; Huilin Wang; Min Chen; Xiaofang Sun; Tak Yeung Leung; Sau Wai Cheung; Kwong Wai Choy Journal: Genet Med Date: 2016-02-25 Impact factor: 8.822
Authors: Stephanie C Y Yu; Peiyong Jiang; Kwong W Choy; Kwan Chee Allen Chan; Hye-Sung Won; Wing C Leung; Elizabeth T Lau; Mary H Y Tang; Tak Y Leung; Yuk Ming Dennis Lo; Rossa W K Chiu Journal: PLoS One Date: 2013-04-17 Impact factor: 3.240