A Para-Bombay Blood Group Case Associated with a Novel FUT1 Mutation c.361G>A

<b><i>Background:</i></b> Here we report a case of para-Bombay phenotype due to a novel mutation <i>FUT1</i> c.361G&#x3e;A p.(Ala121Thr) and a nonfunctional allele <i>FUT1</i>*<i>01N.13</i>(c.881_882delTT) which showed a discrepancy in the routine ABO blood group typing. <b><i>Materials and Methods:</i></b> The ABO phenotype and the Lewis blood group were typed with serological methods. The ABH antigens in saliva were determined by a hemagglutination inhibition test. The CDS region of <i>ABO, FUT1</i>and <i>FUT2</i> were amplified with polymerase chain reaction and then directly sequenced. The novel mutation was confirmed by cloning and sequencing. Three-dimensional (3-D) structural analysis of the mutant and wild-type Fut1 were performed by the Chimera software. <b><i>Results:</i></b> A, B and H antigens were not detected on the surface of red blood cells (RBCs) by the serological technique, and the B and H blood group substances were detected in the saliva, while the Lewis phenotype was Le(a–b+). Sequencing and cloning analysis showed the presence of a novel <i>FUT1</i> mutation c.361G&#x3e;A and a nonfunctional allele <i>FUT1</i>*<i>01N.13</i>(c.881_882delTT). The ABO genotype was <i>ABO</i>*<i>B.01/ABO</i>*<i>O.01.01</i>. The in silico analysis showed that the mutation p.(Ala121Thr) of <i>FUT1</i>did not change the 3-D structure of the whole enzyme but caused a certain amplitude of turnover in the loop region where Ala121 was located. <b><i>Conclusions:</i></b> A novel <i>FUT1</i> allele (<i>FUT1</i>*c.361G&#x3e;A) was identified in a Chinese individual with para-Bombay B phenotype. The <i>FUT1</i>c.361G&#x3e;A mutation may significantly downregulate the expression of H antigens on RBCs by damaging the enzyme conformation.

Influence of ABO Locus on PFA-100 Collagen-ADP Closure Time Is Not Totally Dependent on the Von Willebrand Factor. Results of a GWAS on GAIT-2 Project Phenotypes

(1) Background: In a previous study, we found that two phenotypes related to platelet reactivity, measured with the PFA-100 system, were highly heritable. The aim of the present study was to identify genetic determinants that influence the variability of these phenotypes: closure time of collagen-ADP (Col-ADP) and of collagen-epinephrine (Col-Epi). (2) Methods: As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia (2) Project, 935 individuals from 35 large Spanish families were studied. A genome-wide association study (GWAS) with ≈ 10 M single nucleotide polymorphisms (SNPs) was carried out with Col-ADP and Col-Epi phenotypes. (3) Results: The study yielded significant genetic signals that mapped to the ABO locus. After adjusting both phenotypes for the ABO genotype, these signals disappeared. After adjusting for von Willebrand factor (VWF) or for coagulation factor VIII (FVIII), the significant signals disappeared totally for Col-Epi phenotype but only partially for Col-ADP phenotype. (4) Conclusion: Our results suggest that the ABO locus exerts the main genetic influence on PFA-100 phenotypes. However, while the effect of the ABO locus on Col-Epi phenotype is mediated through VWF and/or FVIII, the effect of the ABO locus on Col-ADP phenotype is partly produced through VWF and/or FVIII, and partly through other mechanisms.