Mutations of the KLF1 gene detected in Japanese with the In(Lu) phenotype

Miho Kawai; Kumi Obara; Takayuki Onodera; Takayuki Enomoto; Kenichi Ogasawara; Hatsue Tsuneyama; Makoto Uchikawa; Shoichi Inaba

doi:10.1111/trf.13990

Mutations of the KLF1 gene detected in Japanese with the In(Lu) phenotype

Transfusion. 2017 Apr;57(4):1072-1077. doi: 10.1111/trf.13990. Epub 2017 Feb 14.

Authors

Miho Kawai¹, Kumi Obara¹, Takayuki Onodera¹, Takayuki Enomoto¹, Kenichi Ogasawara², Hatsue Tsuneyama^{2

3}, Makoto Uchikawa³, Shoichi Inaba¹

Affiliations

¹ Japanese Red Cross Kanto-Koshinetsu Block Saitama Blood Center, Saitama, Japan.
² Japanese Red Cross Central Blood Institute, Tokyo, Japan.
³ Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan.

PMID: 28194794
DOI: 10.1111/trf.13990

Abstract

Background: In(Lu) is characterized by a reduced expression of antigens in the Lutheran blood group system as well as other blood group antigens. Mutations of the erythroid transcription factor, KLF1, have been reported to cause the In(Lu) phenotype, and we investigated Japanese In(Lu) to estimate the prevalence of the phenotype and KLF1 polymorphism.

Study design and methods: Blood samples were screened by monoclonal anti-CD44 and the In(Lu) phenotype was confirmed by tube tests including adsorption and elution tests using anti-Lu^a and anti-Lu^b . KLF1, LU, and A4GALT genes were analyzed by polymerase chain reaction and sequencing.

Results: We identified 100 of 481,322 blood donors (0.02%), and the previously characterized 20 donors, who had the In(Lu) phenotype with the LUB/LUB genotype. A total of 100 of the 120 In(Lu) individuals had mutant KLF1 alleles, and we identified 13 known and 21 novel alleles. The mutant KLF1 alleles with c.947G>A (p.Cys316Tyr), c.862A>G (p.Lys288Glu), or c.968C>G (p.Ser323Trp) were major in the In(Lu) individuals. The P1 antigen of 29 In(Lu) (two P¹ /P¹ , 27 P¹ /P² ) showed significantly weakened expression by hemagglutination.

Conclusions: The prevalence of the In(Lu) phenotype in the Japanese population was 0.02%, and we identified 13 known and 21 novel KLF1 alleles. The KLF1 mutations cause the reduced expression of the P1 antigen.

MeSH terms

Amino Acid Substitution
Asian People
Cell Adhesion Molecules / blood
Cell Adhesion Molecules / genetics*
Female
Galactosyltransferases / biosynthesis
Galactosyltransferases / genetics
Globosides / biosynthesis
Globosides / metabolism
Humans
Japan
Kruppel-Like Transcription Factors / blood
Kruppel-Like Transcription Factors / genetics*
Lutheran Blood-Group System / blood
Lutheran Blood-Group System / genetics*
Male
Mutation, Missense*
Phenotype*

Substances

BCAM protein, human
Cell Adhesion Molecules
Globosides
Kruppel-Like Transcription Factors
Lutheran Blood-Group System
erythroid Kruppel-like factor
galactopyranosyl-1-4-paragloboside
Galactosyltransferases
UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase