title: Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene.
abstract: Peroxisome biogenesis disorders (PBD) are lethal hereditary diseases caused by abnormalities in the biogenesis of peroxisomes. At present, 12 different complementation groups have been identified and to date, all genes responsible for each of these complementation groups have been identified. The peroxisomal membrane protein PEX14 is a key component of the peroxisomal import machinery and may be the initial docking site for the two import receptors PEX5 and PEX7. Although PEX14 mutants have been identified in yeasts and CHO-cells, human PEX14 deficiency has apparently not been documented. We now report the identification of a new complementation group of the peroxisome biogenesis disorders with PEX14 as the defective gene. Indeed, human PEX14 rescues the import of a PTS1-dependent as well as a PTS2-dependent protein into the peroxisomes in fibroblasts from a patient with Zellweger syndrome belonging to the new complementation group. This patient was homozygous for a nonsense mutation in a putative coiled-coil region of PEX14, c.553C>T (p.Q185X). Furthermore, we showed that the patient's fibroblasts lacked PEX14 as determined by immunocytochemical analysis. These findings indicate that there are 13 genotypes in PBD and that the role of PEX14 is also essential in humans.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan. nshim@cc.gifu-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagase
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Koyama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komori
authors.forename: Takashi
authors.initials: T
authors.lastname: Osumi
authors.forename: Gootjes
authors.initials: G
authors.lastname: Jeannette
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts; D005816:Genetic Complementation Test; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D018901:Peroxisomal Disorders / Q000235:genetics*; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015211:Zellweger Syndrome / Q000235:genetics
chemical_list: C000614264:PEX5 protein, human; C000614269:PEX7 protein, human; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear