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Human Mutation Sep 2005Diseases of the Zellweger spectrum represent a major subgroup of the peroxisome biogenesis disorders, a group of autosomal-recessive diseases that are characterized by... (Review)
Review
Diseases of the Zellweger spectrum represent a major subgroup of the peroxisome biogenesis disorders, a group of autosomal-recessive diseases that are characterized by widespread tissue pathology, including neurodegeneration. The Zellweger spectrum represents a clinical continuum, with Zellweger syndrome (ZS) having the most severe phenotype, and neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) having progressively milder phenotypes. Mutations in the PEX1 gene, which encodes a 143-kDa AAA ATPase protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The PEX1 mutations identified to date comprise insertions, deletions, nonsense, missense, and splice site mutations. Mutations that produce premature truncation codons (PTCs) are distributed throughout the PEX1 gene, whereas the majority of missense mutations segregate with the two essential AAA domains of the PEX1 protein. Severity at the two ends of the Zellweger spectrum correlates broadly with mutation type and impact (i.e., the severe ZS correlates with PTCs on both alleles, and the milder phenotypes correlate with missense mutations), but exceptions to these general correlations exist. This article provides an overview of the currently known PEX1 mutations, and includes, when necessary, revised mutation nomenclature and genotype-phenotype correlations that may be useful for clinical diagnosis.
Topics: ATPases Associated with Diverse Cellular Activities; Alleles; Codon; Exons; Genotype; Humans; Membrane Proteins; Models, Genetic; Mutation; Mutation, Missense; Peroxisomes; Phenotype; Polymorphism, Genetic; Zellweger Syndrome
PubMed: 16086329
DOI: 10.1002/humu.20211 -
Journal of Child Neurology Nov 2010A term male newborn was noted to have severe diffuse hypotonia, hyporeflexia, hepatosplenomegaly, and characteristic abnormal facies of Zellweger syndrome, the diagnosis...
A term male newborn was noted to have severe diffuse hypotonia, hyporeflexia, hepatosplenomegaly, and characteristic abnormal facies of Zellweger syndrome, the diagnosis of which was confirmed by identification of 2 mutations including Nt2098insT, a frameshift with premature stop codon in exon 13, as well as a novel second mutation at Nt3038G→A (Arg1013His) on skin fibroblast testing. His brain magnetic resonance imaging (MRI) demonstrated bilateral germinolytic cysts with unilateral hemorrhagic transformation. Germinolytic cysts are one of the characteristic radiographic features of Zellweger syndrome, but germinal matrix hemorrhage has never been reported. Germinal matrix hemorrhage is common in premature infants, but found in only 4% of normal term infants. Germinal matrix hemorrhage was seen in a case of Zellweger syndrome with a novel mutation.
Topics: Brain; Cerebral Hemorrhage; Humans; Infant, Newborn; Magnetic Resonance Imaging; Male; Zellweger Syndrome
PubMed: 20952722
DOI: 10.1177/0883073810365545 -
Journal of Inherited Metabolic Disease 1992A preterm (gestational age 34 weeks), small for gestational age infant (birth weight less than P2,3) is described. Because of unexplained slightly disturbed liver...
A preterm (gestational age 34 weeks), small for gestational age infant (birth weight less than P2,3) is described. Because of unexplained slightly disturbed liver function tests at age 2 months, extensive metabolic examinations were performed. Elevated blood levels of very long-chain fatty acids, pipecolic acid and abnormal levels of bile acid intermediates were detected, suggesting a peroxisomal disorder. The plasmalogen content of erythrocytes was decreased. Morphologically distinct peroxisomes were absent in the liver. In fibroblasts an accumulation of very long-chain fatty acids, decreased activity of acyl-CoA:dihydroxyacetone phosphate acyltransferase and impaired de novo biosynthesis of plasmalogens was found. In summary, a mild variant of the classical cerebro-hepato-renal syndrome of Zellweger was found without the characteristic clinical facial signs.
Topics: Bile Acids and Salts; Fatty Acids; Fibroblasts; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Liver; Male; Microbodies; Zellweger Syndrome
PubMed: 1583879
DOI: 10.1007/BF01800347 -
Journal of Child Neurology Dec 2012Zellweger syndrome (cerebrohepatorenal syndrome) is very rare and is the most severe form of peroxisomal biogenesis disorders. These can be caused by mutations in any of...
Zellweger syndrome (cerebrohepatorenal syndrome) is very rare and is the most severe form of peroxisomal biogenesis disorders. These can be caused by mutations in any of the currently known Peroxin genes and typically present in the neonatal period with multiorgan involvement. Patients usually do not survive beyond 1 year of age. This article reports a case of Zellweger syndrome in a male Native American infant confirmed by clinical findings, imaging studies, and biochemical analysis. Genetic studies show a novel mutation (c.3030G>T, p. Glutamine1010Histidine) altering the last nucleotide of exon 19 in the Peroxin1 (PEX1) gene.
Topics: ATPases Associated with Diverse Cellular Activities; Brain; Exons; Humans; Indians, North American; Infant; Magnetic Resonance Imaging; Male; Membrane Proteins; Mutation; Zellweger Syndrome
PubMed: 22378672
DOI: 10.1177/0883073811435918 -
Biochemical and Biophysical Research... May 2018Mitochondria are constantly communicating with the rest of the cell. Defects in mitochondria underlie severe pathologies, whose mechanisms remain poorly understood. It... (Review)
Review
Mitochondria are constantly communicating with the rest of the cell. Defects in mitochondria underlie severe pathologies, whose mechanisms remain poorly understood. It is becoming increasingly evident that mitochondrial malfunction resonates in other organelles, perturbing their function and their biogenesis. In this manuscript, we review the current knowledge on the cross-talk between mitochondria and other organelles, particularly lysosomes, peroxisomes and the endoplasmic reticulum. Several organelle interactions are mediated by transcriptional programs, and other signaling mechanisms are likely mediating organelle dysfunction downstream of mitochondrial impairments. Many of these organelle crosstalk pathways are likely to have a role in pathological processes.
Topics: AMP-Activated Protein Kinases; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Endoplasmic Reticulum; Gene Expression Regulation; Humans; Lysosomal Storage Diseases; Lysosomes; Mitochondria; Mitochondrial Diseases; Peroxisomes; Signal Transduction; Transcription, Genetic; Zellweger Syndrome
PubMed: 28456629
DOI: 10.1016/j.bbrc.2017.04.124 -
Genetic Counseling (Geneva, Switzerland) 2011Zellweger syndrome is a peroxisomal disorder resulting from the mutations in PEX genes generally presenting in the neonatal period with profound hypotonia seizures,...
Zellweger syndrome is a peroxisomal disorder resulting from the mutations in PEX genes generally presenting in the neonatal period with profound hypotonia seizures, inability to feed, liver cysts with hepatic dysfunction, chondrodysplasia punctata. Kabuki make-up syndrome is a multiple congenital anomalies and mental retardation syndrome with characteristic facial appearance, skeletal abnormalities, dermatoglyphic abnormalities, mental retardation and short stature. Abnormal liver functions and some atypical findings were also reported in some patients with Kabuki syndrome. In this report a case with late onset Zellweger syndrome who had some phenotypical findings which are also seen in Kabuki Syndrome will be presented. The inclusion of Zellweger syndrome into the differential diagnosis of the patients with Kabuki-like phenotype in addition to abnormal liver functions is emphasized.
Topics: Abnormalities, Multiple; Child, Preschool; Diagnosis, Differential; Face; Hematologic Diseases; Humans; Liver; Liver Function Tests; Male; Phenotype; Vestibular Diseases; Zellweger Syndrome
PubMed: 21848015
DOI: No ID Found -
Human Genetics Oct 1988A 16-day-old girl with Zellweger syndrome and a chromosomal rearrangement, 46,XX,del(7)(q11.22q11.23), is reported. The diagnosis was confirmed by marked deficiencies of...
A 16-day-old girl with Zellweger syndrome and a chromosomal rearrangement, 46,XX,del(7)(q11.22q11.23), is reported. The diagnosis was confirmed by marked deficiencies of peroxisomal beta-oxidation enzymes and dihydroxyacetone phosphate acyltransferase activities in rectal cells and fibroblasts obtained by biopsy and in hepatic cells obtained at autopsy. This is the first report of Zellweger syndrome associated with a chromosomal arrangement, a microdeletion of chromosome 7. A tentative gene assignment to 7q11 is suggested.
Topics: Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 7; Female; Humans; Infant, Newborn; Karyotyping; Zellweger Syndrome
PubMed: 3169748
DOI: 10.1007/BF00702873 -
American Journal of Medical Genetics.... Sep 2007Zellweger syndrome (ZS) is an autosomal recessive peroxisomal disorder that results from mutations in one of the peroxisome biogenesis (PEX) genes. This is the first...
Zellweger syndrome (ZS) is an autosomal recessive peroxisomal disorder that results from mutations in one of the peroxisome biogenesis (PEX) genes. This is the first patient reported with uniparental disomy (UPD) resulting in ZS, in this case maternal isodisomy of chromosome 1 involving reduction to homoallelism of a frameshift mutation within PEX 10. Other reported cases of UPD1, and evidence for the imprinting of genes on chromosome 1, are reviewed. The molecular findings in this patient have important implications for molecular testing and genetic counseling in ZS.
Topics: Chromosomes, Human, Pair 1; Female; Genomic Imprinting; Humans; Infant, Newborn; Peroxins; Receptors, Cytoplasmic and Nuclear; Zellweger Syndrome
PubMed: 17702006
DOI: 10.1002/ajmg.a.31912 -
Pediatric Neurology Nov 1995A patient with Zellweger syndrome, who manifested marked dilatation of the lateral ventricles, observed at 34 weeks gestation by fetal ultrasonography, is reported....
A patient with Zellweger syndrome, who manifested marked dilatation of the lateral ventricles, observed at 34 weeks gestation by fetal ultrasonography, is reported. Postnatal magnetic resonance imaging revealed marked colpocephaly and hypogenesis of the posterior part of the corpus callosum. However, pachygyria was limited to the perisylvian regions. Biochemical diagnosis was based on increased serum very-long-chain fatty acids, 2-hydroxysebacic aciduria, and the detection of the ghosts of peroxisomal membrane in cultured fibroblasts. The patient was classified as belonging to group B of this syndrome by complementation study.
Topics: Female; Humans; Infant, Newborn; Magnetic Resonance Imaging; Pregnancy; Ultrasonography, Prenatal; Zellweger Syndrome
PubMed: 8771174
DOI: 10.1016/0887-8994(95)00215-4 -
Pediatric Neurology Sep 2019
Topics: Chondrodysplasia Punctata; Hip Joint; Humans; Peroxisomal Disorders; Radiography; Zellweger Syndrome
PubMed: 31023602
DOI: 10.1016/j.pediatrneurol.2019.03.019