POINT MUTATIONS AND DELETION RESPONSIBLE FOR THE BOMBAY H-NULL AND THE REUNION H-WEAK BLOOD-GROUPS

Objective: Definition of the molecular basis of the Reunion and the Bo mbay red cell and salivary H-deficient phenotypes. Methods: Sequence a nd expression of FUT1 and FUT2 genes from H-deficient individuals. Fam ily segregation analysis of the mutations responsible for the fucosylt ransferase defects of H, secretor and Lewis systems. Results: The Indi an red cell H null Bombay phenotype depends on a new mutation of the F UT1 gene. T725 --> G changing Leu242 --> Arg. Their salivary nonsecret or phenotype is secondary to a complete deletion of the FUT2 gene. The red cell H weak Reunion phenotype depends on another new mutation of FUT1, C349 --> T which induces a change of His117 --> Tyr. Their saliv ary nonsecretor phenotype is due to the known Caucasian inactivating m utation G428 --> A. Conclusion: Single prevalent FUT1 and FUT2 point m utations and a deletion are responsible for the Indian Bombay H null a nd the Reunion H weak phenotypes found on Reunion island. This is in c ontrast with other H-deficient phenotypes where sporadic nonprevalent inactivating mutations are the rule.