IDENTIFICATION OF CLINICALLY SIGNIFICANT, SUBMICROSCOPIC CHROMOSOME ALTERATIONS AND UPD IN FOETUSES WITH ULTRASOUND ANOMALIES USING GENOME WIDE 250K SNP ARRAY ANALYSIS

Brigitte Faas (1) , Ineke van Der Burgt (1) , Angelique Kooper (1) , Rolph Pfundt (1) , Jayne Hehir-Kwa (1) , Arie Smits (1) , Nicole de Leeuw (1)

1 Department of Human Genetics

Background: The implementation of microarray analysis in prenatal diagnostics is a topic of discussion, as rare CNVs with unknown/uncertain clinical consequences are likely to be found. The application of targeted microarrays limits such findings, but the potential disadvantage is that relevant, so far unknown, aberrations might be overlooked. Therefore, we explore the possibilities for the prenatal application of the genome wide 250k SNP array platform. Methods: Affymetrix 250k NspI SNP array analysis was performed on DNA from 38 prenatally karyotyped foetuses with ultrasound anomalies. Analyses were performed after TOP, IUFD, or birth on DNA isolated from foetal or neonatal material. Results: Aberrations were detected in 17/38 foetuses, six of whom with a previously identified chromosomal abnormality and eleven with previously normal or balanced karyotypes. Of the latter, the detected aberration occurred de novo and was considered of clinical relevance in five cases (16%), inherited from a healthy parent in four cases (12%), and de novo yet with unclear clinical relevance in two cases (6%). The clinically relevant abnormalities were either novel copy number variants (CNVs) (N=3) or concerned a uniparental disomy (UPD; N=2). Conclusion: In at least 16% of foetuses with ultrasound anomalies and a normal or balanced karyotype, causal (submicroscopic) aberrations were detected, illustrating the importance of the (careful) implementation of microarray analysis in prenatal diagnosis. The fact that the identified, clinically relevant, aberrations would have gone undetected with most targeted approaches underscores the added value of a genome wide approach.

Mots clés: Diagnostics; Clinical genetics; Cytogenetics; Molecular genetics; Obstetrics and Gynaecology

Brigitte Faas, Ineke van Der Burgt, Angelique Kooper, Rolph Pfundt, Jayne Hehir-Kwa, et al.. IDENTIFICATION OF CLINICALLY SIGNIFICANT, SUBMICROSCOPIC CHROMOSOME ALTERATIONS AND UPD IN FOETUSES WITH ULTRASOUND ANOMALIES USING GENOME WIDE 250K SNP ARRAY ANALYSIS. Journal of Medical Genetics, 2010, 47 (9), pp.586. ⟨10.1136/jmg.2009.075853⟩. ⟨hal-00557389⟩