Next-generation sequencing of 35 RHD variants in 16 253 serologically D− pregnant women in the Finnish population

• Published in: Blood advances 2020-10, Vol.4 (20), p.4994-5001
• Main Authors: Tammi, Silja M., Tounsi, Wajnat A., Sainio, Susanna, Kiernan, Michele, Avent, Neil D., Madgett, Tracey E., Haimila, Katri
• Format: Article
• Language: English
• Subjects: Female; Finland; High-Throughput Nucleotide Sequencing; Humans; Pregnancy; Pregnant Women; Prenatal Diagnosis; Rh-Hr Blood-Group System - genetics; Transfusion Medicine
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020001569

Fetal RHD screening for targeted routine antenatal anti-D prophylaxis has been implemented in many countries, including Finland, since the 2010s. Comprehensive knowledge of the RHD polymorphism in the population is essential for the performance and safety of the anti-D prophylaxis program. During the first 3 years of the national screening program in Finland, over 16 000 samples from RhD− women were screened for fetal RHD; among them, 79 samples (0.5%) containing a maternal variant allele were detected. Of the detected maternal variants, 35 cases remained inconclusive using the traditional genotyping methods and required further analysis by next-generation sequencing (NGS) of the whole RHD gene to uncover the variant allele. In addition to the 13 RHD variants that have been previously reported in different populations, 8 novel variants were also detected, indicating that there is more variation of RHD in the RhD− Finnish population than has been previously known. Three of the novel alleles were identified in multiple samples; thus, they are likely specific to the original Finnish population. National screening has thus provided new information about the diversity of RHD variants in the Finnish population. The results show that NGS is a powerful method for genotyping the highly polymorphic RHD gene compared with traditional methods that rely on the detection of specific nucleotides by polymerase chain reaction amplification. •Eight novel RHD variant alleles have been detected in the Finnish population following NGS of the whole RHD gene.•NGS is a powerful method for genotyping the highly polymorphic RHD gene. [Display omitted]