Biomaterial Database

Genetics and molecular basis of human peroxisome biogenesis disorders. 2012

Hans R Waterham, and Merel S Ebberink

University of Amsterdam, the Netherlands. h.r.waterham@amc.nl

Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of autosomal recessive disorders comprised of two clinically distinct subtypes: the Zellweger syndrome spectrum (ZSS) disorders and rhizomelic chondrodysplasia punctata (RCDP) type 1. PBDs are caused by defects in any of at least 14 different PEX genes, which encode proteins involved in peroxisome assembly and proliferation. Thirteen of these genes are associated with ZSS disorders. The genetic heterogeneity among PBDs and the inability to predict from the biochemical and clinical phenotype of a patient with ZSS which of the currently known 13 PEX genes is defective, has fostered the development of different strategies to identify the causative gene defects. These include PEX cDNA transfection complementation assays followed by sequencing of the thus identified PEX genes, and a PEX gene screen in which the most frequently mutated exons of the different PEX genes are analyzed. The benefits of DNA testing for PBDs include carrier testing of relatives, early prenatal testing or preimplantation genetic diagnosis in families with a recurrence risk for ZSS disorders, and insight in genotype-phenotype correlations, which may eventually assist to improve patient management. In this review we describe the current status of genetic analysis and the molecular basis of PBDs.

UI	MeSH Term	Description	Entries
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011296	Prenatal Diagnosis	Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth.	Diagnosis, Prenatal,Fetal Diagnosis,Fetal Imaging,Fetal Screening,Intrauterine Diagnosis,Antenatal Diagnosis,Antenatal Screening,Diagnosis, Antenatal,Diagnosis, Intrauterine,Prenatal Screening,Antenatal Diagnoses,Antenatal Screenings,Diagnosis, Fetal,Fetal Diagnoses,Fetal Imagings,Fetal Screenings,Imaging, Fetal,Intrauterine Diagnoses,Prenatal Diagnoses,Prenatal Screenings,Screening, Antenatal,Screening, Fetal,Screening, Prenatal
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074183	ATPases Associated with Diverse Cellular Activities	A large highly conserved family of ATPases with diverse functions in cells that are characterized by the presence of a P-LOOP and a ring shape. They couple the energy generated by ATP hydrolysis to remodeling or mechanical translocation of their target molecules.	AAA ATPase,AAA Protease,AAA+ ATPase,AAA+ Protease,AAA ATPases,AAA Proteases,AAA+ ATPases,AAA+ Proteases,ATPase, AAA,ATPase, AAA+,ATPases, AAA+,Protease, AAA,Protease, AAA+,Proteases, AAA,Proteases, AAA+
D000251	Adenosine Triphosphatases	A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.	ATPases,Adenosinetriphosphatase,ATPase,ATPase, DNA-Dependent,Adenosine Triphosphatase,DNA-Dependent ATPase,DNA-Dependent Adenosinetriphosphatases,ATPase, DNA Dependent,Adenosinetriphosphatases, DNA-Dependent,DNA Dependent ATPase,DNA Dependent Adenosinetriphosphatases,Triphosphatase, Adenosine
D056726	Genetic Association Studies	The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.	Candidate Gene Identification,Candidate Gene Analysis,Candidate Gene Association Studies,Candidate Gene Association Study,Gene Discovery,Genotype-Phenotype Association,Genotype-Phenotype Associations,Genotype-Phenotype Correlation,Genotype-Phenotype Correlations,Analyses, Candidate Gene,Analysis, Candidate Gene,Association Studies, Genetic,Association Study, Genetic,Association, Genotype-Phenotype,Associations, Genotype-Phenotype,Candidate Gene Analyses,Correlation, Genotype-Phenotype,Correlations, Genotype-Phenotype,Discovery, Gene,Gene Analyses, Candidate,Gene Analysis, Candidate,Gene Identification, Candidate,Genetic Association Study,Genotype Phenotype Association,Genotype Phenotype Associations,Genotype Phenotype Correlation,Genotype Phenotype Correlations,Identification, Candidate Gene,Studies, Genetic Association,Study, Genetic Association
D018901	Peroxisomal Disorders	A heterogeneous group of inherited metabolic disorders marked by absent or dysfunctional PEROXISOMES. Peroxisomal enzymatic abnormalities may be single or multiple. Biosynthetic peroxisomal pathways are compromised, including the ability to synthesize ether lipids and to oxidize long-chain fatty acid precursors. Diseases in this category include ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; rhizomelic chondrodysplasia (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC); hyperpipecolic acidemia; neonatal adrenoleukodystrophy; and ADRENOLEUKODYSTROPHY (X-linked). Neurologic dysfunction is a prominent feature of most peroxisomal disorders.	Adrenoleukodystrophy, Neonatal,Hyperpipecolic Acidemia,Adrenoleukodystrophy, Autosomal Neonatal Form,Adrenoleukodystrophy, Autosomal, Neonatal Form,Hyperpipecolatemia,Neonatal Adrenoleukodystrophy,Peroxisomal Dysfunction, General,Peroxisomal Dysfunction, Multiple,Peroxisomal Dysfunction, Single,Acidemia, Hyperpipecolic,Acidemias, Hyperpipecolic,Adrenoleukodystrophies, Neonatal,Dysfunction, General Peroxisomal,Dysfunction, Multiple Peroxisomal,Dysfunction, Single Peroxisomal,Dysfunctions, General Peroxisomal,Dysfunctions, Multiple Peroxisomal,Dysfunctions, Single Peroxisomal,General Peroxisomal Dysfunction,General Peroxisomal Dysfunctions,Hyperpipecolic Acidemias,Multiple Peroxisomal Dysfunction,Multiple Peroxisomal Dysfunctions,Neonatal Adrenoleukodystrophies,Peroxisomal Disorder,Peroxisomal Dysfunctions, General,Peroxisomal Dysfunctions, Multiple,Peroxisomal Dysfunctions, Single,Single Peroxisomal Dysfunction,Single Peroxisomal Dysfunctions