Rare Diseases Symptoms Automatic Extraction

Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease.

[neonatal adrenoleukodystrophy]

Peroxisomal matrix protein import requires the action of two AAA ATPases, PEX1 and PEX6. Mutations in either the PEX1 or PEX6 gene are the most common cause of the lethal neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease and account for disease in 80% of all such patients. We report here that overexpression of PEX6 can suppress the phenotypes of certain PEX1-deficient cells, that overexpression of PEX1 can suppress the phenotypes of certain PEX6-deficient cells, and that these instances of suppression are allele-specific and require partial activity of the mutated gene. In addition to genetic evidence for interaction between PEX1 and PEX6, we find that the PEX1 and PEX6 proteins interact in the yeast two-hybrid assay and physically associate with one another in vitro. We previously identified a missense mutation in PEX1, G843D, which attenuates PEX1 function and is the most common cause of these diseases, present in one-third of all such patients. The G843D mutation attenuates the interaction between PEX1 and PEX6 in both the two-hybrid system and in vitro and appears to be suppressed by overexpression of PEX6. We conclude that PEX1 and PEX6 form a complex of central importance to peroxisome biogenesis and that mutations affecting this complex constitute the most common cause of the Zellweger syndrome spectrum of diseases.

Diseases presenting "common cause" symptom

  • achondroplasia
  • acute rheumatic fever
  • adrenomyeloneuropathy
  • allergic bronchopulmonary aspergillosis
  • alpha-thalassemia
  • aniridia
  • aromatase deficiency
  • benign recurrent intrahepatic cholestasis
  • cadasil
  • child syndrome
  • coats disease
  • congenital adrenal hyperplasia
  • congenital toxoplasmosis
  • cushing syndrome
  • erdheim-chester disease
  • esophageal adenocarcinoma
  • esophageal squamous cell carcinoma
  • fabry disease
  • familial hypocalciuric hypercalcemia
  • hydrocephalus with stenosis of the aqueduct of sylvius
  • inclusion body myositis
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • lamellar ichthyosis
  • legionellosis
  • liposarcoma
  • locked-in syndrome
  • malignant atrophic papulosis
  • neonatal adrenoleukodystrophy
  • neuralgic amyotrophy
  • pendred syndrome
  • primary hyperoxaluria type 1
  • pyruvate dehydrogenase deficiency
  • scrub typhus
  • systemic capillary leak syndrome
  • thoracic outlet syndrome
  • typhoid
  • von hippel-lindau disease
  • wiskott-aldrich syndrome
  • zellweger syndrome

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