Novel regulatory variant in ABO intronic RUNX1 binding site inducing A3 phenotype.
Vox Sang
; 119(4): 377-382, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38226545
ABSTRACT
BACKGROUND AND OBJECTIVES:
Mixed-field agglutination in ABO phenotyping (A3, B3) has been linked to genetically different blood cell populations such as in chimerism, or to rare variants in either ABO exon 7 or regulatory regions. Clarification of such cases is challenging and would greatly benefit from sequencing technologies that allow resolving full-gene haplotypes at high resolution. MATERIALS ANDMETHODS:
We used long-read sequencing by Oxford Nanopore Technologies to sequence the entire ABO gene, amplified in two overlapping long-range PCR fragments, in a blood donor presented with A3B phenotype. Confirmation analyses were carried out by Sanger sequencing and included samples from other family members.RESULTS:
Our data revealed a novel heterozygous g.10924C>A variant on the ABO*A allele located in the transcription factor binding site for RUNX1 in intron 1 (+5.8 kb site). Inheritance was shown by the results of the donor's mother, who shared the novel variant and the anti-A specific mixed-field agglutination.CONCLUSION:
We discovered a regulatory variant in the 8-bp RUNX1 motif of ABO, which extends current knowledge of three other variants affecting the same motif and also leading to A3 or B3 phenotypes. Overall, long-range PCR combined with nanopore sequencing proved powerful and showed great potential as an emerging strategy for resolving cases with cryptic ABO phenotypes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sistema del Grupo Sanguíneo ABO
/
Subunidad alfa 2 del Factor de Unión al Sitio Principal
Límite:
Humans
Idioma:
En
Revista:
Vox Sang
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza