Identification of a common PEX1 mutation in Zellweger syndrome.

[neonatal adrenoleukodystrophy]

The Zellweger spectrum of disease , encompassing Zellweger syndrome and the progressively milder phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease , is due to a failure to form functional peroxisomes . Cell fusion complementation studies demonstrated that these diseases are genetically heterogeneous , with two -thirds of all patients lying within a single complementation group , CG 1 . Molecular genetic and cell biology studies have shown that PEX 1 is deficient in many CG 1 patients . However , previous studies have focused on mildly affected patients and there is still no report of two mutant PEX 1 alleles in any Zellweger syndrome patient . Furthermore , mutations in the PMP 70 gene have also been identified in two Zellweger syndrome patients from CG 1 , raising the possibility that CG 1 patients may represent a mixture of PEX 1 -deficient and PMP 70 -deficient individuals . To address the molecular basis of disease in Zellweger syndrome patients from CG 1 , we examined all 24 PEX 1 exons in four patients , including both patients that have mutations in PMP 70 . PEX 1 mutations were detected in all four patients , including a 1 -bp insertion (c .2097 insT ) in exon 13 that was present in three of the four patients . Subsequent studies demonstrated that this mutation is present in one -half of all CG 1 patients and correlates with the Zellweger syndrome phenotype . As this mutation leads to a loss of protein function its frequency makes it the most common cause of Zellweger syndrome , helping to explain the high percentage of patients that belong to CG 1 .

Diseases
Validation

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

You can validate or delete this automatically detected symptom