Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.

[neonatal adrenoleukodystrophy]

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 PEX 2 (official symbol , PXMP 3 ), two novel mutations in PEX 6 , two novel mutations in PEX 10 , one novel mutation in PEX 12 , and one novel mutation in PEX 13 .

Diseases
Validation

Diseases presenting "rhizomelia" symptom

neonatal adrenoleukodystrophy

zellweger syndrome

This symptom has already been validated