Identification of Nucleotide Substitution in Gene Encoding [Leu^A3]Insulin in Third Japanese Family

We previously described a new case of abnormal insulinemia in Japan. In one allele, nucleotide-sequence analysis revealed a substitution in the codon for the third position of insulin A chain (GTG→TTG), causing [Leu^A3]insulin. This point mutation is the same as that found in insulin Wakayama. In this family, the mutant insulin allele cosegregated with an 850-base pair PvuII allele of the hypervariable region 5′-flanking the insulin gene.