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Identification of two functionally deficient plasma α3‐fucosyltransferase ( FUT6 ) alleles
Author(s) -
Elmgren Anders,
Börjeson Cecilia,
Mollicone Rosella,
Oriol Rafael,
Fletcher Anne,
Larson Göran
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200012)16:6<473::aid-humu4>3.0.co;2-t
Subject(s) - fucosyltransferase , allele , biology , genetics , mutation , point mutation , microbiology and biotechnology , allele frequency , gene
One Indonesian individual without detectable plasma α3‐fucosyltransferase activity was identified with three point mutations, 730C>G (L244V), 907C>G (R303G), and 370C>T (P124S), in the coding region of one FUT6 allele. Another individual, expressing weak plasma α3‐fucosyltransferase activity, had the 907C>G together with the 370C>T mutation, but did not have the 730C>G mutation. PCR‐RFLP analyses of complete families confirmed the segregation of these alleles and illustrated the existence and inheritance of the [370C>T; 907C>G] mutated allele in three additional families. Altogether, this allele was found heterozygously in nine Indonesian and two Swedish individuals, all with detectable plasma α3‐fucosyltransferase activities. The FUT6 allele with the three mutations (370C>T; 730C>G; 907C>G) was identified heterozygously in only two Indonesian individuals, both having the inactivating 739G>A mutation in the other allele and both lacking plasma α3‐fucosyltransferase activity. Enzyme studies made on transiently transfected COS‐7 cells demonstrated that the combination of the 370C>T, 730C>G and 907C>G mutations decreased the V max by more than 80%, but caused no obvious change of the apparent K m values for GDP‐fucose and Gal‐ N ‐acetyllactosamine. In comparison, chimeric constructs with the isolated 730C>G or 907C>G mutations decreased the V max values by about two thirds and one third, respectively. Hum Mutat 16:473–481, 2000. © 2000 Wiley‐Liss, Inc.