Alternative titles; symbols
SNOMEDCT: 115681005;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.2 | [Blood group, Landsteiner-Wiener] | 111250 | 3 | ICAM4 | 614088 |
A number sign (#) is used with this entry because LW blood group antigens reside on a protein encoded by the ICAM4 gene (614088) on chromosome 19p13.
The LW blood group antigens reside on a 42-kD red cell intercellular adhesion molecule designated ICAM4 (Bailly et al., 1994; Bailly et al., 1995).
Sistonen (1984) showed that the LW locus is closely linked to C3 (120700) and Lutheran (111200) on chromosome 19. The maximum lod score was 3.61 at theta = 0.00 for LW:C3 and 3.67 at theta = 0.05 for LW:Lu. The data suggested that the Lewis blood group locus is situated outside the C3-LW region.
Using a C3 DNA probe, Lewis et al. (1987) found no recombinants between LW and C3 (maximum lod score = 4.216 at theta = 0.00). No recombinants were found in 16 female meioses. Combined with the data of Sistonen (1984), the recombination fraction between LW and C3 was estimated to be 0.09 in females (maximum lod score = 3.773).
Lewis et al. (1988) established close linkage between LW and LDLR (606945); maximum lod = 8.43 at theta = 0.00. They concluded that LDLR, C3, and LW constitute a tightly linked gene cluster. Their findings supported a 19p13.2-cen position for LW.
The LW locus was assigned to 19p13.3 by isotopic in situ hybridization (Hermand et al., 1995).
LW(a)/LW(b) Polymorphism
Hermand et al. (1995) demonstrated that the molecular basis for the LW(a)/LW(b) polymorphism is a single-basepair change (308A-G) in the ICAM4 gene that correlates with a PvuII restriction site and results in a gln70-to-arg (Q70R) amino acid substitution (614088.0001). COS-7 cells transfected with LW(a) or LW(b) cDNAs reacted with human anti-LW(a) and anti-LW(b) sera, respectively, as well as with a murine monoclonal anti-LW(ab) antibody, as shown by flow cytometry analysis. Study by Southern blot analysis indicated that the LW locus is composed of a single gene that is not grossly rearranged in the rare LW(a-b-) individuals or in Rh-null individuals deficient for LW antigens. RFLP analysis using PvuII indicated that these variants were homozygous for a phenotypically silent LW(a) allele in all cases.
LW(a-b-) Phenotype
Individuals with the rare LW(a-b-) phenotype lack LW antigens and LW protein expression on red blood cells. Some of these individuals express normal Rh antigens, but others also lack Rh and Rh-associated antigens and proteins. Using Southern blot analysis, Hermand et al. (1995) showed that the ICAM4 gene was not grossly rearranged in an individual with the LW(a-b-) phenotype or in individuals with the Rh-null phenotype, who also lack LW antigens. RFLP analysis using PvuII indicated that the LW(a-b-) individual and 3 Rh-null individuals were homozygous for a phenotypically silent LW(a) allele.
In an individual with the LW(a-b-) phenotype who carried a normal Rh phenotype, Hermand et al. (1996) identified a 10-bp deletion in exon 1 of the ICAM4 gene (614088.0002) that generated a premature stop codon, resulting in a truncated protein without the transmembrane and cytoplasmic domains. Heterogeneity was indicated by the fact that no detectable abnormality of the LW gene or transcript could be detected in another LW(a-b-) individual.
LW stands for Landsteiner and Wiener, the researchers who first discovered the LW blood group with antibody raised in guinea pigs injected with the cells of rhesus monkeys. It was originally thought to be identical to the anti-D first described in a woman with an erythroblastotic infant studied by Levine and Stetson (1939). Hence, the name of the Rh system. It was later found to be distinct; LW is the true Rhesus blood group, but this designation had been preempted. Levine suggested the designation LW.
Bailly, P., Hermand, P., Callebaut, I., Sonneborn, H. H., Khamlichi, S., Mornon, J.-P., Cartron, J.-P. The LW blood group glycoprotein in homologous to intercellular adhesion molecules. Proc. Nat. Acad. Sci. 91: 5306-5310, 1994. [PubMed: 8202485] [Full Text: https://doi.org/10.1073/pnas.91.12.5306]
Bailly, P., Tontti, E., Hermand, P., Cartron, J.-P., Gahmberg, C. G. The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. Europ. J. Immun. 25: 3316-3320, 1995. [PubMed: 8566017] [Full Text: https://doi.org/10.1002/eji.1830251217]
Hermand, P., Gane, P., Mattei, M. G., Sistonen, P., Cartron, J.-P., Bailly, P. Molecular basis and expression of the LW(a)/LW(b) blood group polymorphism. Blood 86: 1590-1594, 1995. [PubMed: 7632968]
Hermand, P., Le Pennec, P. Y., Rouger, P., Cartron, J.-P., Bailly, P. Characterization of the gene encoding the human LW blood group protein in LW(+) and LW(-) phenotypes. Blood 87: 2962-2967, 1996. [PubMed: 8639917]
Levine, P., Stetson, R. E. An unusual case of intragroup agglutination. JAMA 113: 126-127, 1939.
Lewis, M., Kaita, H., Coghlan, G., Philipps, S., Belcher, E., McAlpine, P. J., Coopland, G. R., Woods, R. A. The chromosome 19 linkage group LDLR, C3, LW, APOC2, LU, SE in man. Ann. Hum. Genet. 52: 137-144, 1988. [PubMed: 2907851] [Full Text: https://doi.org/10.1111/j.1469-1809.1988.tb01089.x]
Lewis, M., Kaita, H., Philipps, S., Coghlan, G., McAlpine, P. J., Coopland, G. R., Woods, R. A. The LW:C3 recombination fraction in female meioses. Ann. Hum. Genet. 51: 201-203, 1987. [PubMed: 3120637] [Full Text: https://doi.org/10.1111/j.1469-1809.1987.tb00872.x]
Race, R. R., Sanger, R. Blood Groups in Man. (6th ed.) Oxford: Blackwell (pub.) 1975. Pp. 228-232.
Sistonen, P. Linkage of the LW blood group locus with the complement C3 and Lutheran blood group loci. Ann. Hum. Genet. 48: 239-242, 1984. [PubMed: 6431896] [Full Text: https://doi.org/10.1111/j.1469-1809.1984.tb01020.x]
Sistonen, P., Virtaranta-Knowles, K. Evidence for linkage of LW blood group locus with the complement C3, and Le, Lu and Se loci with assignment to chromosome 19. (Abstract) Cytogenet. Cell Genet. 40: 747, 1985.