title: Genetic heterogeneity of peroxisome biogenesis disorders among Japanese patients: evidence for a founder haplotype for the most common PEX10 gene mutation.
abstract: We, as the only diagnostic center for peroxisome biogenesis disorders (PBD) in Japan, identified a total of 31 Japanese patients with PBD during the last 20 years. They were 27 patients with Zellweger syndrome (ZS), including two sib cases, three with neonatal adrenoleukodystrophy (NALD) and one with rhizomelic type chondrodysplasia punctata (RCDP). No patient with infantile Refsum disease has been detected. These patients were genetically subdivided into complementation group A (five ZS and one NALD), B (11 ZS), C (four ZS), E (five ZS and two NALD), F (two ZS), and R (one RCDP). They were subjected to mutation analysis of PEX1, PEX2, PEX6, PEX7, and PEX10. All the 11 ZS patients with group-B PBD had a common mutation, i.e., a homozygous 2-base-pair deletion in PEX10. To determine whether this highly frequent mutation is due to a founder effect, we analyzed single nucleotide polymorphisms within PEX10 among patients and Japanese controls. The mutation apparently arose once on an ancestral chromosome in the Japanese population. Based on the value of 24 PBD patients identified during the last 10 years, we estimated the prevalence of PBD in Japan to be approximately one in 500,000 births.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan. nshim@cc.gifu-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagase
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000235:genetics; D000483:Alleles; D002806:Chondrodysplasia Punctata / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D000074401:Peroxins; D000074428:Peroxisomal Biogenesis Factor 2; D018901:Peroxisomal Disorders / Q000235:genetics*; D000074437:Peroxisomal Targeting Signal 2 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015211:Zellweger Syndrome / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C116156:PEX10 protein, human; C000614230:PEX2 protein, human; C000614269:PEX7 protein, human; D000074401:Peroxins; D000074437:Peroxisomal Targeting Signal 2 Receptor; C000614232:Pex2 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D000074428:Peroxisomal Biogenesis Factor 2; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490759:PEX6 protein, human; C096998:Pex6 protein, rat