A novel nonsense mutation of the PEX7 gene in a patient with rhizomelic chondrodysplasia punctata

Abstract

Mutations in the PEX7 gene encoding a peroxisome targeting signal 2 (PTS2) were identified in two patients with rhizomelic chondrodysplasia punctata (RCDP). A 7-year-old girl, the first Japanese individual to be diagnosed biochemically as a case of RCDP, had a novel nonsense mutation, R232ter, in the PEX7 gene, which had been inherited from her consanguineous parents. Another patient, a Chilean boy with RCDP, had compound heterozygous mutations of PEX7, L292ter and A218V, both of which have been documented. R232ter, which deletes all of the last two WP40 repeats in the PEX7 gene, is sufficient to inactivate functions of the PEX7 gene.

Defective lipid remodeling of GPI anchors in peroxisomal disorders, Zellweger syndrome, and rhizomelic chondrodysplasia punctata

“…GPI lipid remodeling to generate 1-alkyl-2-acyl GPI is defective in PEX7 mutant CHO cells and fi broblasts from patients with RCDP type 1 PEX7 is required for transporting proteins bearing a PTS2, such as alkyl-DHAP synthase, into the peroxisome and is a causal gene for RCDP type 1 (24)(25)(26)(27). We tested whether a defect in PEX7 affects the lipid remodeling of GPI.…”

“…Fibroblast cell lines defective in PEX7, termed Gifu R01 and R03, were derived from two patients with RCDP type 1; those defective in PEX5, termed 2-07, and those defective in PEX16, termed D-01, were from patients with ZS; those defective in DHAP-AT, termed NL-#2 and #3, and those defective in alkyl-DHAP synthase, termed NL-#5 and #6, were from patients with RCDP type 2 and patients with RCDP type 3, respectively ( 24,54 ). This study was approved by internal review committees in the Research Institute for Microbial Diseases of Osaka University, Gifu University School of Medicine, and University of Amsterdam.…”

Enfermedad peroxisomal, condrodisplasia rizomelica punctata tipo 1: reporte de caso

“…The manifestation RCDP1 disease includes ocular problems, as cataracts 11 , as well as weight and height with symmetrical rhizomelyc shortening 4 , seizures, cortical and cerebellar atrophy 12 , congenital contractures and dysmorphic facial features. Regarding punctate calcifications of the cartilage, although they constitute a key radiological finding, they are temporary and they will not be evident after the first or second year of life 13 .…”

“…PEX genes encode a series of proteins called peroxins, essential in the process of forming peroxisomes. These include peroxisomal targeting signal peptides, PTS1 and PTS2, which work as intermediaries in the importation of proteins into the peroxisome 4,5 .…”

“…This enzyme takes part of the oxidation of fatty acids, with the subsequent accumulation of its substrate, phytanic acid. Another enzyme, acyldihydroxyacetone phosphate synthase (ADHAPS), is also affected in the disease, causing the decrease of its product, plasmalogens [4][5][6] .…”