Peroxisome disorders: Zellweger Spectrum and Related Single Enzyme Defects

Research Genetic test

offered by

Braverman Laboratory

GTR Test Accession: GTR000520399.3

INHERITED DISEASEMETABOLIC DISEASENERVOUS SYSTEM ... View more

Last updated in GTR: 2023-01-04

Last annual review date for the lab: 2023-01-04 Past due

At a Glance

Conditions (1):

Peroxisome biogenesis disorder

Genes (20):

ACAA1 (3p22.2); ACBD5 (10p12.1); ACOX1 (17q25.1); AMACR (5p13.2); HSD17B4 (5q23.1) more...

Study description:

To determine the mutation spectrum for Peroxisome Biogenesis Disorders and …

Recruitment status:

Currently open

Eligibility criteria:

Not provided

Methods (3):

Biochemical Genetics - Analyte: Liquid chromatography-tandem mass spectrometry (LC-MS/MS); ...

Study Description

Name:

Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD) and Related Peroxisome Disorders

Study short name:

Peroxisome Disorders

ClinicalTrials.gov identifier:

NCT01668186

Protocol number:

11-090-PED

Test purpose:

Contribute to generalizable knowledge

Description:

To determine the mutation spectrum for Peroxisome Biogenesis Disorders and related peroxisome disorders, correlate this with phenotype and develop therapeutic options. For this goal we are performing mutation analysis of PEX and related genes, evaluating protein functions, looking at peroxisome metabolite biomarkers and reviewing medical records and imaging studies. We … View more

View citations (10)

The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. Steinberg S, et al. Mol Genet Metab. 2004;83(3):252-63. doi:10.1016/j.ymgme.2004.08.008. PMID: 15542397.
Hormonal responsiveness by immature rabbit uterine epithelial cells polarized in vitro. Mani SK, et al. Endocrinology. 1991;128(3):1563-73. doi:10.1210/endo-128-3-1563. PMID: 1705507.
Steinberg SJ, Snowden A, Braverman NE, Chen L, Watkins PA, Clayton PT, Setchell KD, Heubi JE, Raymond GV, Moser AB, Moser HW. A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts. J Inherit Metab Dis. 2009;32(1):109-19. doi:10.1007/s10545-008-0969-8. Epub 2008 Dec 25. PMID: 19127411.
Zhang R, Chen L, Jiralerspong S, Snowden A, Steinberg S, Braverman N. Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds. Proc Natl Acad Sci U S A. 2010;107(12):5569-74. doi:10.1073/pnas.0914960107. Epub 2010 Mar 08. PMID: 20212125.
Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations. Dranchak PK, et al. J Cell Biochem. 2011;112(5):1250-8. doi:10.1002/jcb.22979. PMID: 21465523.
Levesque S, Morin C, Guay SP, Villeneuve J, Marquis P, Yik WY, Jiralerspong S, Bouchard L, Steinberg S, Hacia JG, Dewar K, Braverman NE. A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population. BMC Med Genet. 2012;13:72. doi:10.1186/1471-2350-13-72. Epub 2012 Aug 15. PMID: 22894767.
Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives. Braverman NE, et al. Dev Disabil Res Rev. 2013;17(3):187-96. doi:10.1002/ddrr.1113. PMID: 23798008.
Hiebler S, Masuda T, Hacia JG, Moser AB, Faust PL, Liu A, Chowdhury N, Huang N, Lauer A, Bennett J, Watkins PA, Zack DJ, Braverman NE, Raymond GV, Steinberg SJ. The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder. Mol Genet Metab. 2014;111(4):522-532. doi:10.1016/j.ymgme.2014.01.008. Epub 2014 Jan 23. PMID: 24503136.
Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Dodt G, et al. Nat Genet. 1995;9(2):115-25. doi:10.1038/ng0295-115. PMID: 7719337.
The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor. Yahraus T, et al. EMBO J. 1996;15(12):2914-23. PMID: 8670792.

Study type:

Observational study

Offered by:

Braverman Laboratory

View lab's website

Person responsible for the study:

Nancy Braverman, MD, MS, Lab Director

Study contact:

Nancy Braverman, MD, MS, Lab Director

nancy.braverman@mcgill.ca

514-934-1934 ext 23404

Research contact policy:

by health professional only

Participation

Recruitment status:

Currently open

Consent form:

Not provided

Recommended fields not provided:

Eligibility criteria

Conditions

Total conditions: 1

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 20

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 3

Method Category

Test method

Instrument

Analyte

Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Other

Immunohistochemistry

peroxisome import assessment on skin fibroblasts

Sequence analysis of the entire coding region

Sanger

Technical Information

Test Procedure:

DNA, RNA sequencing Mass spec C26:0 lysoPC, plasmalogen and bile acids PEX protein amounts by immunoblotting Peroxisome import by immunohistochemistry

View citations (3)

Levesque S, Morin C, Guay SP, Villeneuve J, Marquis P, Yik WY, Jiralerspong S, Bouchard L, Steinberg S, Hacia JG, Dewar K, Braverman NE. A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population. BMC Med Genet. 2012;13:72. doi:10.1186/1471-2350-13-72. Epub 2012 Aug 15. PMID: 22894767.
MacLean GE, Argyriou C, Di Pietro E, Sun X, Birjandian S, Saberian P, Hacia JG, Braverman NE. Zellweger spectrum disorder patient-derived fibroblasts with the PEX1-Gly843Asp allele recover peroxisome functions in response to flavonoids. J Cell Biochem. 2019;120(3):3243-3258. doi:10.1002/jcb.27591. Epub 2018 Oct 26. PMID: 30362618.
Fallatah W, Schouten M, Yergeau C, Di Pietro E, Engelen M, Waterham HR, Poll-The BT, Braverman N. Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata. J Inherit Metab Dis. 2021;44(4):1021-1038. doi:10.1002/jimd.12349. Epub 2021 Jan 26. PMID: 33337545.

Test Confirmation:

Combine molecular and functional testing

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View PEX6 variations in ClinVar

View PEX12 variations in ClinVar

View PEX16 variations in ClinVar

Practice guidelines:

Consumer resources:

MedlinePlusGenetics (GHR)

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

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