IDENTIFICATION OF 2 MUTANT ALLELES OF TRANSCOBALAMIN-II IN AN AFFECTED FAMILY

Transcobalamin II(TC II) deficiency is a rare autosomal recessive dise ase leading to cobalamin (Cbl;Vitamin B-12) deficiency characterized b y failure to thrive, megaloblastic anemia, impaired immunodefence and neurological manifestations. By means of Southern blotting and sequenc e analysis of TC II cDNA amplified from fibroblasts of an affected chi ld and his parents, we have identified two mutant TC II alleles, one w ith a gross deletion and the other with a 4 nucleotide deletion. Both the mutations caused TC II mRNA and protein deficiency and hence defec tive plasma transport of Cbl and the development of Cbl deficiency in the affected child. The present study has identified molecular defects that cause TC II deficiency and lead to intracellular Cbl deficiency in humans.