Noninvasive Prenatal Diagnosis of a Case of Down Syndrome due to Robertsonian Translocation by Massively Parallel Sequencing of Maternal Plasma DNA

Abstract

To the Editor: There has been much recent interest in the use of massively parallel sequencing of maternal plasma DNA for the detection of fetal Down syndrome, or trisomy 21 (1–4). DNA fragments in maternal plasma were sequenced at random to determine if an additional dose of chromosome 21 (chr21)1 sequences was contributed by the fetus. This approach has been shown to be highly robust in distinguishing trisomic and euploid cases. In these studies, however, all recruited trisomy 21 cases possess supernumerary whole chr21, as confirmed by karyotyping. This approach has not been formally shown to be applicable to other forms of the condition. For example, although the ratio of fetal to maternal DNA in maternal plasma has been shown to remain relatively constant across the entire genome for normal chromosomes (5), it is unknown whether an aberrant chromosome (e.g., one containing a chromosomal translocation) would exhibit an atypical genomic representation in the plasma. As a first step in addressing this issue, we applied the sequencing approach to a case of familial robertsonian translocation. This study was approved by the local research ethics committee. Maternal peripheral blood samples …