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A novel non-invasive prenatal sickle cell disease test for all at-risk pregnancies

Research output: Contribution to journalArticlepeer-review

Julia van Campen, Lee Silcock, Shu Yau, Yvonne Daniel, Joo Wook Ahn, Caroline Ogilvie, Kathy Mann, Eugene Oteng-Ntim

Original languageEnglish
Pages (from-to)119-124
Number of pages6
JournalBritish Journal of Haematology
Issue number1
Published1 Jul 2020

King's Authors


Sickle cell disease (SCD) is the most common genetic haematological disorder. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived procedure-related miscarriage risk. We report the development of a targeted massively parallel sequencing (MPS) assay for the NIPD of fetal SCD using fetal cell-free (cf)DNA from maternal plasma, with no requirement for paternal or proband samples. In all, 64 plasma samples from pregnant women were analysed: 42 from SCD carriers, 15 from women with homozygous (Hb SS) SCD and seven from women with compound heterozygous (Hb SC) SCD. Our assay incorporated a relative mutation dosage assay for maternal carriers and a wild type allele detection assay for affected women (Hb SS/Hb SC). Selective analysis of only smaller cfDNA fragments and modifications to DNA fragment hybridisation capture improved diagnostic accuracy. Clinical sensitivity was 100% and clinical specificity was 100%. One sample with a fetal fraction of <4% was correctly called as ‘unaffected’, but with a discordant genotype (Hb AA rather than Hb AS). Six samples gave inconclusive results, of which two had a fetal fraction of <4%. This study demonstrates that NIPD for SCD is approaching clinical utility.

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