Novel Mutations in the PEX2 Gene of Four Unrelated Patients with a Peroxisome Biogenesis Disorder

Gootjes, Jeannette; Elpeleg, Orly; Eyskens, François; Mandel, Hanna; Mitanchez, Delphine; Shimozawa, Nobuyuki; Suzuki, Yasuyuki; Waterham, Hans R.; Wanders, Ronald J. A.

doi:10.1203/01.pdr.0000106862.83469.8d

Cited by 22 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One mutation in the PEX2 gene (c.355C>T) was found to be associated with temperature sensitivity: cells cultured at 30°C show partial catalase import [Imamura et al, 1998b]. The patient fibroblasts homozygous for the c.669G>A mutation displayed a mosaic peroxisomal pattern, characterized by import competency of catalase in 30% of the cells [Gootjes et al, 2003, 2004a]. In three different cell lines, sequence analysis of exon 4 identified only one heterozygous mutation (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder

Ebberink¹,

Mooijer²,

Gootjes³

et al. 2010

Hum. Mutat.

Self Cite

133

103

View full text Add to dashboard Cite

The autosomal recessive Zellweger syndrome spectrum (ZSS) disorders comprise a main subgroup of the peroxisome biogenesis disorders and can be caused by mutations in any of 12 different currently identified PEX genes resulting in severe multisystemic disorders. To get insight into the spectrum of PEX gene defects among ZSS disorders and to investigate if additional human PEX genes are required for functional peroxisome biogenesis, we assigned over 600 ZSS fibroblast cell lines to different genetic complementation groups. These fibroblast cell lines were subjected to a complementation assay involving fusion by means of polyethylene glycol or a PEX cDNA transfection assay specifically developed for this purpose. In a majority of the cell lines we subsequently determined the underlying mutations by sequence analysis of the implicated PEX genes. The PEX cDNA transfection assay allows for the rapid identification of PEX genes defective in ZSS patients. The assignment of over 600 fibroblast cell lines to different genetic complementation groups provides the most comprehensive and representative overview of the frequency distribution of the different PEX gene defects. We did not identify any novel genetic complementation group, suggesting that all PEX gene defects resulting in peroxisome deficiency are currently known.

show abstract

Section: Resultsmentioning

confidence: 99%

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder

Ebberink¹,

Mooijer²,

Gootjes³

et al. 2010

Hum. Mutat.

Self Cite

133

103

View full text Add to dashboard Cite

show abstract

“…PEX2 is an integral membrane protein with two transmembrane domains (transmembrane domain 1 (TMD1): amino acid (AA)140-159, TMD2: AA195-213) and a RING finger motif (AA144-283) at the C-terminal end (Gootjes, et al, 2004). c.115C>T mutation in patient PBD-HR1 leads to the introduction of a termination codon at Gln39, which generates a truncated protein lacking both transmembrane domains.…”

Section: Resultsmentioning

confidence: 99%

“…PEX2 gene was the first gene identified to be mutated in Zellweger spectrum patients and eight homozygous mutations have been found so far (Gootjes, et al, 2004;Shimozawa, et al, 1993;Shimozawa, et al, 1992;Steinberg, et al, 2004). PEX2 is an integral membrane protein with two transmembrane domains (transmembrane domain 1 (TMD1): amino acid (AA)140-159, TMD2: AA195-213) and a RING finger motif (AA144-283) at the C-terminal end (Gootjes, et al, 2004). c.115C>T mutation in patient PBD-HR1 leads to the introduction of a termination codon at Gln39, which generates a truncated protein lacking both transmembrane domains.…”

Section: Resultsmentioning

confidence: 99%

Identification of novel mutations inPEX2,PEX6,PEX10,PEX12, andPEX13in Zellweger spectrum patients

et al. 2006

View full text Add to dashboard Cite

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 PEX2 (official symbol, PXMP3), two novel mutations in PEX6, two novel mutations in PEX10, one novel mutation in PEX12, and one novel mutation in PEX13.

show abstract

“…The clinical phenotype of these two patients strongly differs from PBD patients with PEX2 gene mutations who may display cerebellar symptoms in addition to other severe neurological signs in the context of Zellweger spectrum disorders [12,13]. …”

Section: Discussionmentioning

confidence: 99%

Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

Sevin

Ferdinandusse

Waterham

et al. 2011

Orphanet J Rare Dis

Self Cite

View full text Add to dashboard Cite

ObjectiveTo expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA).Case reportTwo brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of blood peroxisomal markers strongly suggested a peroxisomal biogenesis disorder. Sequencing of candidate PEX genes revealed a homozygous c.865_866insA mutation in the PEX2 gene leading to a frameshift 17 codons upstream of the stop codon. PEX gene mutations usually result in a severe neurological phenotype (Zellweger spectrum disorders).ConclusionsGenetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA.

show abstract

Novel Mutations in the PEX2 Gene of Four Unrelated Patients with a Peroxisome Biogenesis Disorder

Cited by 22 publications

References 34 publications

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder

Identification of novel mutations inPEX2,PEX6,PEX10,PEX12, andPEX13in Zellweger spectrum patients

Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

Contact Info

Product

Resources

About