The Discovery of Unbalanced Translocations through Genome-Wide cfDNA Testing [32R]

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Abstract

INTRODUCTION:

The MaterniT® GENOME test reports on genome-wide copy number variations >7Mb, making it uniquely positioned to identify deletions and duplications, such as those in unbalanced translocations. Since late 2015, more than 28,000 MaterniT® GENOME samples have been ordered. Here we describe cases where unbalanced translocations have been discovered.

METHODS:

Maternal blood samples submitted for genome-wide cfDNA testing were subjected to DNA extraction, library preparation, and whole-genome massively parallel sequencing as described by Jensen et al. Sequencing data were analyzed using a novel algorithm as described by Lefkowitz et al.

RESULTS:

A total of 28,760 samples were submitted to the clinical laboratory and 1,392 (4.8%) of these resulted positive. Among all positives, 49 were interpreted as possible translocation events between two chromosomes. Fetal confirmation was reported in 59% with an additional 37% likely concordant given family or clinical history, there were two cases (4%) lost to follow up and zero reported discordant cases. Prior knowledge of parental translocation existed for 29%, while 16% were identified as follow up to cfDNA testing. A minority of cases (6%) were de novo, with the remaining subset pending full parental assessment (51%). Totals will be updated prior to final publication.

CONCLUSION:

Familial translocations not previously amenable to cfDNA screening may now benefit from early identification or added reassurance. New discovery of families at risk of carrying a translocation often helps explain past pregnancy complications, as well as clarify future reproductive risk. MaterniT® GENOME is a relevant screening tool for families with a known translocation or suggestive family history.

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