Different inactivating mutations in the LU genes of three individuals with the Lutheran-null phenotype.
BACKGROUND
The null phenotype of the Lutheran blood group system, Lu(null) 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. Lu(null) of the recessive type appears to result from homozygosity for an inactive LU gene.


METHODS
Three unrelated recessive Lu(null) 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 Lu(null). 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 Lu(null) phenotype, each encoding Lutheran glycoproteins with a disrupted structure.
Karamatic Crew
Vanja
V
Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK.
Mallinson
Gary
G
Green
Carole
C
Poole
Joyce
J
Uchikawa
Makoto
M
Tani
Yoshihiko
Y
Geisen
Christof
C
Oldenburg
Johannes
J
Daniels
Geoff
G
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008188:Lutheran Blood-Group System / Q000235:genetics; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D012698:Serologic Tests
C090228:BCAM protein, human; D015815:Cell Adhesion Molecules; D008188:Lutheran Blood-Group System; D009363:Neoplasm Proteins