The Lutheran inhibitor blood group phenotype (In(Lu)) is characterized phenotypically by the apparent absence of the Lu antigen (BCAM; 612773) on red blood cells during serologic tests, i.e., Lu(a-b-). Since it is inherited as an autosomal dominant trait, ... The Lutheran inhibitor blood group phenotype (In(Lu)) is characterized phenotypically by the apparent absence of the Lu antigen (BCAM; 612773) on red blood cells during serologic tests, i.e., Lu(a-b-). Since it is inherited as an autosomal dominant trait, it was initially postulated to result from an inhibitor of the Lu antigen. However, Singleton et al. (2008) found that the phenotype results from a mutation in the transcription factor KLF1 that regulates expression of the BCAM gene. The Lu-null phenotype, or autosomal recessive true Lu(a-b-) (247420), is caused by homozygous or compound heterozygous inactivating mutations in the BCAM gene.
By flow cytometry, Helias et al. (2013) demonstrated that the majority of red blood cells from individuals with the In(Lu) blood type completely lacked BCAM reactivity, although a small proportion showed some BCAM reactivity, suggesting weak expression of ... By flow cytometry, Helias et al. (2013) demonstrated that the majority of red blood cells from individuals with the In(Lu) blood type completely lacked BCAM reactivity, although a small proportion showed some BCAM reactivity, suggesting weak expression of Lu(b). In addition, In(Lu) blood cells also showed low expression of CD44 (107269) compared to controls. These flow cytometric parameters allowed distinction of In(Lu) from recessive true Lu-null cells, or Lu(a-b-), that is caused by inactivating mutations in the BCAM gene. All 10 samples of In(Lu) carried heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0007-600599.0009). Helias et al. (2013) also found that In(Lu) individuals had increased levels of fetal hemoglobin (HbF) (mean of 2.14%) compared to controls (mean less than 1.0%), and slightly increased levels of HbA2 (141850). Finally, 9 In(Lu) individuals who were heterozygous for the P1 allele (607922.0007) did not express the P1 antigen (see 111400), whereas 1 who was homozygous for the P1 allele expressed only weak P1. These findings suggested that the expression of P1 is suppressed in the In(Lu) blood type. Helias et al. (2013) concluded that the KLF1 haploinsufficiency has different effects on the expression of different erythroid proteins, likely reflecting the variable dependence of their respective genes on the KLF1 transcription factor.
Karamatic Crew et al. (2007) noted that the autosomal dominant Lu(a-b-) is more common than autosomal recessive Lu(a-b-) (247420).
Singleton et al. (2008) identified 9 different heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0001-600599.0004) ... Karamatic Crew et al. (2007) noted that the autosomal dominant Lu(a-b-) is more common than autosomal recessive Lu(a-b-) (247420). Singleton et al. (2008) identified 9 different heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0001-600599.0004) in 21 of 24 persons with the autosomal dominant In(Lu) phenotype. The individuals had no reported pathology, indicating that 1 functional KLF1 allele is sufficient to sustain human erythropoiesis. In red blood cell samples from 10 probands with the dominant In(Lu) phenotype, Helias et al. (2013) identified 10 different heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0001-600599.0002 and 600599.0007-600599.0009).