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

Abstract

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.

Clinical and genetic features of lysinuric protein intolerance in Japan

“…Following our identification of two mutations in SLC7A7 in three Japanese LPI patients, 7 11 patients from seven different families in northern Japan were found to be homozygous for the p.R410* mutation. 8,9 This is a founder effect mutation unique to Japan; as such, it has been assumed that many Japanese LPI patients would have a distinct genetic background compared with patients from other countries, but this has not yet been directly tested. Furthermore, it is currently unknown as to whether the clinical manifestations of Japanese LPI are distinct from those of other ethnicities.…”

SP-D counteracts GM-CSF-mediated increase of granuloma formation by alveolar macrophages in lysinuric protein intolerance

“…LPI is relatively frequent in Finland and Italy [46,47], and in Japan, 1:119 individuals are heterozygous carriers for this LPI gene mutations with estimated frequency of 1:50000 individuals living with LPI [48]. LPI has also been reported in other countries where variable penetrance of specific founder mutations was shown to be responsible for the disease [37,49]; hence, many LPI individuals with SLC7A7 mutations may be misdiagnosed.…”

Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment

“…12 Lysinuric protein intolerance is more prevalent in Finland (1 in 60 000) than elsewhere in the world due to Finnish disease heritage, but several patients have been reported from, for example, Italy, Tunisia, and Japan. 13,14 LPI is caused by bi-allelic mutations in the gene SLC7A7, which encodes the y + LAT1 protein, the catalytic light chain subunit of the heteromeric amino acid transporter. [15][16][17][18] All the Finnish patients share the same mutation, a substitution of T for A at cDNA position 1181-2A →T (LPI Fin ).…”