A cluster of lysinuric protein intolerance (LPI) patients in a northern part of Iwate, Japan due to a founder effect

Lysinuric protein intolerance is an autosomal recessive disease characterized by defective transport of the dibasic aminoacids. Mutational analysis of LPI patients in the northern part of Japan revealed that six were homozygous for the R410X mutation and two others were compound heterozygotes of R410X and other unknown mutations. In the population epidemiology study in a local cluster in the northern part of Iwate, ten heterozygotes were found in 1190 newborn babies leading to an estimated LPI incidence of 1/57,000. Polymorphism analysis revealed two major alleles, A and B, in intron 8. While the population frequency of allele A was 0.9 and that of allele B was 0.1 in the northern part of Japan the R410X mutations were exclusively on allele B in 31 chromosomes suggesting a founder effect. Genetic analysis in patients revealed strong linkage disequilibrium with D14S283 and TCRA indicating that the R410X mutation occurred before at least 130 generations ago (about 2600 years). The R410X mutation was shown to be useful as a molecular marker for screening LPI patients in the northern part of Japan. Hum Mutat 16:270–271, 2000. © 2000 Wiley-Liss, Inc.