Identification of new KLF1 and LU alleles during the resolution of Lutheran typing discrepancies

García‐Sánchez, Félix; Pardi, Cecilia; Kupatawintu, Pawinee; Thornton, Nicole; Rodriguez, Miguel-Angel; Lucea, Irene; Sood, Chhavi; Ochoa‐Garay, Gorka

doi:10.1111/trf.13556

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…Eernstman et al [32] recorded that the c.304T>C distribution was in concordance with the frequencies observed in European populations, showing no correlation with the expression of CD44, band 3, Lu a , Lu b , HbF, and HbA2. In the current finding, we identified the c.304T>C variant with missense and frameshift variants, as mentioned above, which is in consonance with a previously published study of one Thai donor, c.[304T>C, 484insC] [25]. In contrast, homozygosity of the c.304T>C variant identified in the remaining donor did not seem to be a significant cause for the In(Lu) phenotype in this cohort.…”

Section: Discussionsupporting

confidence: 92%

Identification of Lutheran Blood Groups and Genetic Variants within KLF1 among Thai Blood Donors

Intharanut

Khumsuk

Nathalang

2023

Transfus Med Hemother

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Background: Lua and Lub are inherited as codominant allelic characters resulting from a single nucleotide variant (SNV) of the basal cell adhesion molecule (BCAM) gene. Red cells of the dominantly inherited suppressor of the Lutheran antigens In(Lu) phenotypically appear as Lu(a−b–) by the haemagglutination test. In(Lu) resulted from heterozygosity for mutations within the erythroid-specific Krüppel-like factor 1 (KLF1) gene. This study aimed to determine the frequency of the Lu(a) and Lu(b) phenotypes and genotypes and genetic variants of the distinct In(Lu) among Thai blood donors. Material and Methods: Samples from 334 Thai donors were phenotyped with anti-Lua and anti-Lub. These DNA samples and an additional 1,370 donor DNA samples with unknown Lu(a)/Lu(b) phenotypes were genotyped using an in-house PCR-SSP. In the case of the three Lu(a–b–) donors, the BCAM and KLF1 genes were analysed by PCR and sequencing. Results: A total of 331 of the 334 donors were Lu(a–b+), while the other observed phenotype, appearing as Lu(a–b–), was found among three donors. Of those three Lu(a–b–) donors with the LU*02/02 genotype, we identified KLF1 variant alleles, consisting of two variants: c.[304T>C, 1001C>G] and c.[304T>C, 519_525dupCGGCGCC], leading to the In(Lu) phenotype, and one homozygous variant (c.304T>C) mutation. Also, only one Thai donor was genotyped as LU*01/02, confirmed by serology test and DNA sequencing. Conclusion: In this study, we identified KLF1 variants to be included in Lutheran typing analysis in Thai populations. Therefore, the application of genotyping and phenotyping methods has simultaneously been in use to screen and confirm the rare Lu(a+) and In(Lu) phenotypes.

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Section: Discussionsupporting

confidence: 92%

Identification of Lutheran Blood Groups and Genetic Variants within KLF1 among Thai Blood Donors

Intharanut

Khumsuk

Nathalang

2023

Transfus Med Hemother

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“…Red blood cells (RBCs) with the In(Lu) phenotype appeared to reduce other RBC antigens, Indian (CD44 glycoprotein), P1, I, and AnWj. To date, more than 30 different KLF1 alleles responsible for the In(Lu) phenotype have been reported . In this study, we investigated Japanese individuals with the In(Lu) phenotype to understand the molecular basis of the phenotype.…”

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

Kawai¹,

Obara²,

Onodera³

et al. 2017

Transfusion

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“…11 To date, more than 60 alleles associated with benign In(Lu) phenotypes have been reported. [12][13][14][15] Here, we describe our findings from investigation of seven cases referred to our laboratories: six with a Lu(a-b-) phenotype including the historical index case 3 and one referred from a patient subsequently diagnosed with CDA.…”

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confidence: 99%

Novel mutations in KLF1 encoding the In(Lu) phenotype reflect a diversity of clinical presentations

et al. 2017

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BACKGROUND Mutation in the KLF1 gene is the cause of the In(Lu) (Inhibitor of Lutheran) Lu(a–b–) phenotype and more than 60 alleles have been associated with this phenotype. Here we describe findings from investigation of seven cases: six presenting with a Lu(a–b–) phenotype including the historical index case and one referred from a patient with chronic anemia. STUDY DESIGN AND METHODS Serologic testing was by standard methods. DNA testing included amplification and sequencing of KLF1 and LU coding regions. A StuI polymerase chain reaction–restriction fragment length polymorphism was designed to target c.304T>C in KLF1. RESULTS Five different KLF1 alleles were identified. Three are new: KLF1*90A (p.Trp30Ter), KLF*911A (p.Thr304Lys), and KLF1*304C,318G (p. Ser102Pro, Tyr106Ter) present in two unrelated individuals. Two, including the index case, had c.954dupG (p.Arg319Glufs*34), that is, KLF1*BGM06. The child with unexplained anemia had c.973G>A (p.Glu325Lys), associated with congenital dyserythropoietic anemia. The common c.304T>C was found in two of the seven samples investigated and in 60 of 100 blood donors. CONCLUSION Mutations in KLF1 are pleiotropic and although most are benign, others are associated with hematologic abnormalities. We report three new KLF1 alleles associated with benign In(Lu) and document both the molecular basis of the original In(Lu) phenotype using a frozen sample stored for more than 50 years and the cause of unexplained anemia in a child. We also confirm previous observations that c.304C (p.102Pro) is not, by itself, associated with an In(Lu) phenotype in donors self‐identified as U.S. minorities.

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Identification of new KLF1 and LU alleles during the resolution of Lutheran typing discrepancies

Abstract: Besides confirming common phenotypes and detecting rare antigen-negative phenotypes, the use of molecular methods in blood donor typing can prompt the identification of new alleles through discrepancy resolution.

Cited by 6 publications

References 7 publications

Identification of Lutheran Blood Groups and Genetic Variants within KLF1 among Thai Blood Donors

Identification of Lutheran Blood Groups and Genetic Variants within KLF1 among Thai Blood Donors

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

Novel mutations in KLF1 encoding the In(Lu) phenotype reflect a diversity of clinical presentations

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