Single-nucleotide polymorphism-based chromosomal microarray analysis provides clues and insights into disease...

Area of Science:

• Prenatal genetics
• Genomic diagnostics
• Fetal medicine

Background:

• Chromosomal microarray analysis (CMA) is standard for prenatal diagnosis of fetal malformations, identifying microdeletion/duplication syndromes.
• Single-nucleotide polymorphism (SNP)-based CMA offers potential for broader diagnostic capabilities.

Purpose of the Study:

• To evaluate the additional utility of SNP-based CMA in prenatal diagnosis.
• To demonstrate its capability in identifying monogenic diseases, imprinting disorders, and uniparental disomy (UPD).

Main Methods:

• CMA was performed on 6995 pregnancies with fetal malformations using Affymetrix CytoScan arrays.
• Four complex cases illustrating the diagnostic utility of SNP-based CMA were analyzed.

Main Results:

• Identified a microdeletion causing Bloom syndrome in one fetus.
• Diagnosed Kagami-Ogata syndrome (imprinting disorder) in a second fetus.
• Detected deletions associated with Prader-Willi/Angelman syndrome and maternal UPD of chromosome 11 in two other cases.

Conclusions:

• Prenatal CMA, utilizing oligo and SNP platforms, significantly increases diagnostic yield.
• It enables detection of a wider spectrum of genetic disorders, including complex etiologies beyond copy number variants.