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Double heterozygous RhAG mutations causing regulator-type Rhnull phenotype.

Wangxia Li1, Junchao Cai2, Xian Huang3

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|December 28, 2025
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Summary
This summary is machine-generated.

Rhnull, the rarest blood type, presents transfusion challenges. This study identifies a new RhAG genetic mutation causing Rhnull, offering crucial guidance for managing this rare blood type.

Keywords:
Gene mutationsHeterozygous mutationsHomozygous mutationsRhAGRhnull

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Area of Science:

  • Hematology
  • Genetics
  • Immunology

Background:

  • Rhnull is an extremely rare blood type globally.
  • Individuals with Rhnull blood type face significant transfusion difficulties, especially if they develop antibodies.

Purpose of the Study:

  • To determine the genetic cause of regulator-type Rhnull in a healthy donor.
  • To provide transfusion recommendations based on genetic findings.

Main Methods:

  • Performed serology, Sanger sequencing, and long-read sequencing of RhD, RhCE, and RhAG genes.
  • Analyzed the donor and their family members.

Main Results:

  • The donor has Rhnull with typical RhD/CE genes but two novel RhAG mutations (c.419A>C and c.1108G>A).
  • Family members carrying one mutation (c.419A>C) exhibit standard blood types, confirming recessive inheritance.
  • Computational modeling suggests these mutations impair RhAG-RhCE complex formation.

Conclusions:

  • A novel RhAG allele causing Rhnull has been identified and is heritable.
  • Recommends autologous blood storage and comprehensive RhAG genotyping for Rhnull individuals to prevent transfusion complications.