Nonsense mutations in human transcobalamin II deficiency

Abstract

Reverse transcription-polymerase chain reaction has been used to amplify, clone and sequence transcobalamin II (TC II) cDNA from fibroblasts of three unrelated TC II deficient patients who had undetectable TC II protein and mRNA in their fibroblasts (Li et al., Biochem. J, 301, 585-590, 1994). One child of a consanguineous marriage contained a single nucleotide deletion at position 258 in both alleles, while the child from unrelated parents revealed a nonsense mutation at position 1206 in one allele and a single nucleotide deletion at position 483 in the other allele. Both the single nucleotide deletion mutations caused a frameshift and introduced a premature termination codon (indirect nonsense mutations). No mutation was detected in TC II cDNA from the third patient. Based on these results we suggest that TC II deficiency due to lack of TC II protein/mRNA in these patients is due to heterogeneous types of nonsense mutations.