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GENATLAS PHENOTYPE
last update : 12-1-2015
Symbol ZWS1
Location 7q21.2
Name Zellweger cerebrohepatorenal syndrome
Other name(s) peroxisome biogenesis disorder, complementation group 1
Corresponding gene PEX1
Other symbol(s) PBD, ZS, ZSS
Main clinical features
  • facial dysmorphism, ocular abnormalities, severe hypotonia and neonatal seizures
  • also common: renal cysts, hepatomegaly, punctuate calcifications, adrenal lamellar inclusions
  • early death
    • Genetic determination autosomal recessive
    Related entries PBD1, IRD7, NALD
    Function/system disorder metabolism/lipoprotein-lipid
    multisystem/generalized
    Type disease
    Gene product
    Name a 143-kDa AAA ATPase protein required for peroxisome biogenesis
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types     The PEX1 mutations identified to date comprise insertions, deletions, nonsense, missense, and splice site mutations.
    missense   abnormal protein/loss of function the majority of missense mutations segregate with the two essential AAA domains of the PEX1 protein
    various types   truncated protein Mutations that produce premature truncation codons (PTCs) are distributed throughout the PEX1 gene,
    Remark(s)
  • The Zellweger spectrum (ZSS) represents a clinical continuum, with Zellweger syndrome (ZS) having the most severe phenotype, and neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) having progressively milder phenotypes; mutations in the PEX1 gene are the most common cause of the Zellweger spectrum diseases
    • Genotype/Phenotype correlations
  • severity at the two ends of the ZSS correlates broadly with mutation type and impact (i.e., the severe ZS correlates with PTCs on both alleles, and the milder phenotypes correlate with missense mutations), but exceptions to these general correlations exist
  • exonic PEX1 mutation correlates with patient survival (PMID: 21846392))