Discordant prenatal and postnatal RhD typing caused by a novel RHD frameshift variant (c.540del; p. Leu181CysfsTer48 ) in Swedish individuals
Year: 2026
Type: article
Study design: Case Report
Abstract: BACKGROUND AND OBJECTIVES: Non-invasive prenatal testing (NIPT) for fetal RHD genotyping is widely used to guide anti-D prophylaxis, but discrepancies between predicted fetal RhD status and postnatal serological typing can occur due to variant RHD alleles. This study aimed to confirm and characterize a suspected novel exon 4 deletion in RHD using multiple molecular methods and to assess inheritance. MATERIALS AND METHODS: NIPT predicted an RhD-positive fetus in an RhD-negative pregnant woman, whereas postnatal serology showed an RhD-negative phenotype. Molecular analysis of RHD was performed using the RBC-Ready Gene CDE kit (Inno-Train, Kronberg, Germany), targeted next-generation sequencing (NGS) and Sanger sequencing in the family and in an unrelated RhD-negative woman. RESULTS: Targeted NGS identified a single-nucleotide deletion in the RHD gene (c.540del), predicted to result in a frameshift and premature termination (p.Leu181CysfsTer48). Sanger sequencing confirmed the variant in the newborn and demonstrated paternal inheritance, with the father heterozygous for the deletion. The same variant was also identified in an unrelated RhD-negative woman of Swedish origin; notably, the newborn's father was also of Swedish origin. CONCLUSION: This case illustrates a limitation of current NIPT approaches, which detect RHD sequences but not gene functionality. Molecular follow-up is crucial in cases of discordant RhD typing.
Source: Vox Sanguinis
DOI: 10.1111/vox.70351
Authors: Ahlam Badri, Dan Gratschev, Tove Johansson, Agneta Wikman, Tesfai Emahazion
Institutions: Karolinska University Hospital, Karolinska Institutet
Language: English
Topic: Blood groups and transfusion
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,150
OpenAlex ID: W7203868704