Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs.
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.
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Malgorzata I
MI
Srebniak
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Karin Em
KE
Diderich
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Marieke
M
Joosten
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Lutgarde Cp
LC
Govaerts
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Jeroen
J
Knijnenburg
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Femke At
FA
de Vries
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Marjan
M
Boter
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Debora
D
Lont
Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.|Foundation Prenatal Screening Southwest region of the Netherlands, Rotterdam, The Netherlands.
Maarten Fcm
MF
Knapen
Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
Merel C
MC
de Wit
Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
Attie Tji
AT
Go
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Robert-Jan H
RJ
Galjaard
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Diane
D
Van Opstal
D000649:Amniocentesis; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005333:Fetus / Q000000981:diagnostic imaging* / Q000473:pathology; D005820:Genetic Testing; D006801:Humans; D033162:Incidental Findings; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D016216:Ultrasonography, Prenatal