Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders.

[neonatal adrenoleukodystrophy]

Peroxisome biogenesis disorders , including Zellweger syndrome (ZS ), neonatal adrenoleukodystrophy (NALD ) and infantile Refsum disease , are lethal hereditary diseases caused by abnormalities in peroxisomal assembly . To date , 12 genotypes have been identified . We now have evidence that the complete human cDNA encoding Pex 13 p , an SH 3 protein of a docking factor for the peroxisome targeting signal 1 receptor (Pex 5 p ), rescues peroxisomal matrix protein import and its assembly in fibroblasts from PBD patients of complementation group H . In addition , we detected mutations on the human PEX 13 cDNA in two patients of group H . A severe phenotype of a ZS patient (H-02 ) was homozygous for a nonsense mutation , W 234 ter , which results in the loss of not only the SH 3 domain but also the putative transmembrane domain of Pex 13 p . A more mildly affected NALD patient (H-01 ), whose fibroblasts showed the temperature-sensitive (TS ) phenotype , was homozygous for a missense mutation in the SH 3 domain of Pex 13 p , I 326 T . This mutant PEX 13 cDNA expression in a PEX 13 -defective CHO mutant showed I 326 T to be a TS mutation and thus suggested that Pex 13 p with the I 326 T mutation in the SH 3 domain is stable at 30 degrees C but is somewhat unstable at 37 degrees C .

Diseases
Validation

Diseases presenting "severe phenotype" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

cystinuria

dentin dysplasia

dentinogenesis imperfecta

harlequin ichthyosis

hirschsprung disease

hydrocephalus with stenosis of the aqueduct of sylvius

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

neonatal adrenoleukodystrophy

oligodontia

triple a syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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