This report describes peroxisome biogenesis disorder 10A (PBD10A), which is a subtype of peroxisome biogenesis disorder; PBD10A exhibits autosomal recessive inheritance. The human gene implicated in this disease is PEX3, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex3, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
A transgenic construct carrying a cDNA of Hsap\PEX3 has been introduced into flies. Heterologous rescue (functional complementation) of the peroxisome loss phenotype of Dmel\Pex3 null mutants has been demonstrated.
Amorphic mutations of Dmel\Pex3 are lethal in the larval stage. For loss-of-function mutations, observed phenotypes include aspects similar to the human disease, including reduced body size, reduced lifespan, elevated very long chain fatty acid (VLCFA) levels, and a failure to assemble functional peroxisomes.
[updated Apr. 2017 by FlyBase; FBrf0222196]
Newborns affected with Zellweger syndrome (ZS) are hypotonic, feed poorly, and have distinctive facies, seizures, and liver cysts with hepatic dysfunction. Bony stippling of the patella(e) and other long bones may occur. The neurological defects include demyelination, retinal dystrophy, hearing loss and seizures. Infants with ZS are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Older children have retinal dystrophy, sensorineural hearing loss, developmental delay with hypotonia, and liver dysfunction. The clinical courses of the milder forms of peroxisome biogenesis disorder, neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), are variable and may include developmental delays, hearing loss, vision impairment, liver dysfunction, episodes of hemorrhage, and intracranial bleeding. While some children can be very hypotonic, others learn to walk and talk. The condition is often slowly progressive [from GeneReviews, Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.09.09].
PBD syndrome is characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction. There are 4 main phenotypic classes of PBDs that were defined prior to the molecular characterization; three of them in order of severity, Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), form a spectrum of overlapping features. The most severely affected patients with classic Zellweger syndrome die within the first year. Zellweger syndrome is indicated by the "A" in the OMIM subtype designation; the less severe forms are indicated with a "B" in the OMIM subtype designation (BSC). The fourth class, rhizomelic chondrodysplasia punctata (RCDP1), displays a distinct PBD phenotype. [from MIM:214100; 15.08.10]
[PEROXISOME BIOGENESIS DISORDER 10A (ZELLWEGER); PBD10A](https://omim.org/entry/614882)
[PEROXISOME BIOGENESIS FACTOR 3; PEX3](https://omim.org/entry/603164)
Mutations in Hsap\PEX3 are associated exclusively with the most severe phenotype in the peroxisome biogenesis disorder spectrum (Zellwegers syndrome). [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.08.10]
PBD10A is one of a group of peroxisome biogenesis disorders that presents in infants with severe seizures, profound hypotonia, and inability to feed; additional characteristics are craniofacial and eye abnormalities, neuronal migration defects, enlarged liver, small size, and bone abnormalities. Affected individuals do not show significant development and usually die in the first year. [from MIM:614882; 15.08.10]
PBD10A is autosomal recessive and is caused by mutations in the Hsap\PEX3 gene. [from MIM:614882; 15.08.10]
Peroxisomal membrane formation is completely absent in cell lines from individuals with mutations in HSap\PEX3 (peroxisome biogenesis disorder 10A). [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.08.10]
Hsap\PEX3 is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum; Gene_cards:PEX3, 2015.08.10]
PBD10A is is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. [from MIM:614882; 15.08.10]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene PEX3 (1 Drosophila to 1 human). Dmel\Pex3 shares 34% identity and 52% similarity with human PEX3.
