title: Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.
abstract: Mutations in each of the 13 identified human PEX genes are known to cause a peroxisomal biogenesis defect (PBD). Affected patients can be divided into two broad clinical spectra: the Zellweger spectrum, which accounts for about 80% of PBD patients, and the rhizomelia chondrodysplasia punctata (RCDP) spectrum. The clinical continuum of Zellweger spectrum patients extends from Zellweger syndrome (ZS) as the prototype and the most severe entity of this group to neonatal adrenoleukodystrophy (NALD) as an intermediate form and infantile Refsum (IRD) disease as the mildest variant. Characteristic features of ZS patients are dysmorphic features, severe neurological impairment, liver dysfunction, and eye and skeletal abnormalities. Similar but less severe clinical signs are seen in patients with NALD and IRD. In this study ten clinically and/or biochemically well-characterized patients with classical ZS were investigated for defects in all known human PEX genes. We identified two novel mutations in PEX2 (official symbol, PXMP3), two novel mutations in PEX6, two novel mutations in PEX10, one novel mutation in PEX12, and one novel mutation in PEX13.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Krause
authors.forename: Hendrik
authors.initials: H
authors.lastname: Rosewich
authors.forename: Melissa
authors.initials: M
authors.lastname: Thanos
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D000074401:Peroxins; D000074428:Peroxisomal Biogenesis Factor 2; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D015211:Zellweger Syndrome / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C116156:PEX10 protein, human; C105251:PEX12 protein, human; C101884:PEX13 protein, human; C000614230:PEX2 protein, human; D000074401:Peroxins; D018160:Receptors, Cytoplasmic and Nuclear; D000074428:Peroxisomal Biogenesis Factor 2; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490759:PEX6 protein, human