Genetic Heterogeneity in Japanese Patients with Peroxisome Biogenesis Disorders and Evidence for a Founder Haplotype for the Most Common Mutation in PEX10 Gene

Abstract

We have identified 31 Japanese patients with peroxisome biogenesis disorders (PBDs) for 20 years as the only PBDs diagnostic center in Japan: 27 patients with Zellweger syndrome (ZS), including 2 siblings cases, 3 with neonatal adrenoleukodystrophy (NALD) and 1 with rhizomelic type chondrodysplasia punctata (RCDP). No patient with infantile Refsum disease has been detected. In genetical, those were subdivided into complementation group A (5 ZS and 1 NALD), B (11 ZS), C (4 ZS), E (5 ZS and 2 NALD), F (2 ZS) and R (1 RCDP) and mutation analysis of PEX 1, 2, 6, 7 and 10 has been done in these patients. We demonstrated all 11 ZS patients from group B had a common mutation, 2 base pair deletion in PEX 10 gene, homozygously. To determine whether the high frequency of the PEX 10 mutation is due to a founder effect, we analyzed three single nucleotide polymorphisms in the PEX 10 gene among the patients and Japanese controls, which suggested that this mutation arose once on an ancestral chromosome in the Japanese population. We detected 24 PBDs patients in the last 10 years, which means that the incidence of the PBDs in Japan was estimated to be approximately 1 in 500,000 births.