C86Y: as a destructive homozygous mutation deteriorating Pex7p function causing rhizomelic chondrodysplasia punctata type I

Rhizomelic Chondrodysplasia Punctata (RCDP) type 1 is a peroxisomal biogenesis disorder with a genetic abnormality in PEX7 gene. In the present study, mutational analysis was performed on two Iranian RCDP patients with distinct clinical phonotype. Mutation detection was carried out by sequencing of RT-PCR product consisting the whole length of PEX7 cDNA. Sequence data revealed the same missense homozygous mutation of G to A at nucleotide 257 in exon3 of PEX7 coding sequence in both patients. Moreover, genomic analysis of the PEX7 gene confirmed the RT-PCR data. This mutation caused one amino acid residue substitution of Cys to Tyr at codon 86 located on WD1 repeat domain region of Pex7p, which severely affected the functionality of PEX7 protein. Back-transfection of vector encoding mutant Pex7p did not restore the normal peroxisomal function in RCDP patient's fibroblast cells dissimilar to the native type of PEX7.