BACKGROUND: The null phenotype of the Lutheran blood group system, Lunull or Lu(a–b–), is characterized by the lack of all Lutheran system antigens. It can arise from three genetic backgrounds: recessive, dominant, or X-linked. Lunull of the recessive type appears to result from homozygosity for an inactive LU gene.
STUDY DESIGN AND METHODS: Three unrelated recessive Lunull individuals were assessed by standard serologic tests. All exons of the LU gene were directly sequenced from amplified genomic DNA. The validity of the observed mutations within the LU gene was confirmed by the use of either restriction enzymes or allele-specific primers.
RESULTS: All three individuals had the serologic characteristics of recessive Lunull. One individual was doubly heterozygous for a nonsense mutation 691C>T in exon 6 (Arg231STOP) and a deletion of LU exons 3 and 4. The other two samples showed homozygous nonsense mutations: one had 711C>A in exon 6 (Cys237STOP) and the other 361C>T in exon 3 (Arg121STOP).
CONCLUSIONS: The results revealed four unique genetic backgrounds from three examples of the rare recessive Lunull phenotype, each encoding Lutheran glycoproteins with a disrupted structure.