Single nucleotide polymorphism (SNP) based chromosomal microarray analysis provides clues and insights into disease mechanisms.

BACKGROUND: Chromosomal microarray analysis (CMA) in pregnancy is the modality of choice for prenatal diagnosis of fetal malformations, diagnosing microdeletion/duplication syndromes. We demonstrate further utilities of CMA, by diagnosing monogenic disease, imprinting disorders and uniparental disomy (UPD).

METHODS: We performed CMA using Affymetrix CytoScan array for 6995 pregnancies for all indications since November 2013 in a tertiary referral hospital.

RESULTS: Four fetuses had an unforeseen CMA result, shedding light on the clinical presentation. In fetus (1), examined due to intrauterine growth restriction, CMA revealed a 75kbp maternally-inherited microdeletion encompassing the BLM gene. A diagnosis of Bloom syndrome was applied upon identifying a paternally-inherited common founder Ashkenazi mutation. In fetus (2) extremely abnormal maternal serum analytes led to the identification of a deletion in 14q32.2q32.31, on the maternally-inherited copy, diagnosing Kagami-Ogata syndrome known to be an imprinting disorder. Fetus (3) had amniocentesis because of late-onset macrosomia and mild polyhydramnion. A deletion encompassing the locus of Prader-Wili/Angleman syndrome was detected. Fetus (4) had amniocentesis following maternal CMV seroconversion. Maternal UPD of the entire long arm of chromosome 11 was detected.

CONCLUSIONS: Prenatal CMA based on oligo and SNP platforms increase the yield and spectrum of diagnosed disorders beyond just the determination of copy number variants. This article is protected by copyright. All rights reserved.