TY - JOUR
T1 - Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs
AU - Srebniak, Gosia
AU - Diderich, Karin
AU - Joosten, Marieke
AU - Govaerts, LCP
AU - Knijnenburg, Jeroen
AU - Vries, Femke
AU - Boter, Marjan
AU - Lont, Debora
AU - Knapen, Maarten
AU - Wit, Charlotte
AU - Go, Attie
AU - Galjaard, Robert-Jan
AU - Opstal, D
PY - 2016
Y1 - 2016
N2 - To evaluate the diagnostic value of single-nucleotide polymorphism (SNP) array testing in 1033 fetuses with ultrasound anomalies we investigated the prevalence and genetic nature of pathogenic findings. We reclassified all pathogenic findings into three categories: causative findings; unexpected diagnoses (UD); and susceptibility loci (SL) for neurodevelopmental disorders. After exclusion of trisomy 13, 18, 21, sex-chromosomal aneuploidy and triploidies, in 76/1033 (7.4%) fetuses a pathogenic chromosome abnormality was detected by genomic SNP array: in 19/1033 cases (1.8%) a microscopically detectable abnormality was found and in 57/1033 (5.5%) fetuses a pathogenic submicroscopic chromosome abnormality was detected. 58% (n=44) of all these pathogenic chromosome abnormalities involved a causative finding, 35% (n=27) a SL for neurodevelopmental disorder, and 6% (n=5) a UD of an early-onset untreatable disease. In 0.3% of parental samples an incidental pathogenic finding was encountered. Our results confirm that a genomic array should be the preferred first-tier technique in fetuses with ultrasound anomalies. All UDs involved early-onset diseases, which is beneficial for the patients to know. It also seems that UDs occur at a comparable frequency among microscopic and submicroscopic pathogenic findings. SL were more often detected than in pregnancies without ultrasound anomalies.
AB - To evaluate the diagnostic value of single-nucleotide polymorphism (SNP) array testing in 1033 fetuses with ultrasound anomalies we investigated the prevalence and genetic nature of pathogenic findings. We reclassified all pathogenic findings into three categories: causative findings; unexpected diagnoses (UD); and susceptibility loci (SL) for neurodevelopmental disorders. After exclusion of trisomy 13, 18, 21, sex-chromosomal aneuploidy and triploidies, in 76/1033 (7.4%) fetuses a pathogenic chromosome abnormality was detected by genomic SNP array: in 19/1033 cases (1.8%) a microscopically detectable abnormality was found and in 57/1033 (5.5%) fetuses a pathogenic submicroscopic chromosome abnormality was detected. 58% (n=44) of all these pathogenic chromosome abnormalities involved a causative finding, 35% (n=27) a SL for neurodevelopmental disorder, and 6% (n=5) a UD of an early-onset untreatable disease. In 0.3% of parental samples an incidental pathogenic finding was encountered. Our results confirm that a genomic array should be the preferred first-tier technique in fetuses with ultrasound anomalies. All UDs involved early-onset diseases, which is beneficial for the patients to know. It also seems that UDs occur at a comparable frequency among microscopic and submicroscopic pathogenic findings. SL were more often detected than in pregnancies without ultrasound anomalies.
U2 - 10.1038/ejhg.2015.193
DO - 10.1038/ejhg.2015.193
M3 - Article
C2 - 26328504
SN - 1018-4813
VL - 24
SP - 645
EP - 651
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 5
ER -