This report describes peroxisome biogenesis disorder 12A (PBD12A), which is a subtype of peroxisome biogenesis disorder. The human gene implicated in this disease is PEX19, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex19, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
For loss-of-function mutations in the Dmel\Pex19 gene, observed phenotypes include aspects similar to the human disease, including a failure to assemble functional peroxisomes, however it appears that the role of Dmel/Pex19 in peroxisome biogenesis is different from that of Pex19 orthologues in other organisms.
Work in Drosophila has implicated a subset of peroxide proteins, including Pex19, in additional roles in regulation of lipid storage. A Drosophila cell line that carries a knockout mutation in Pex19, S2R+-Pex19-KO-A1 (FBtc0000306), has been used to characterize the role of a subset of Pex proteins in regulating lipid storage.
[updated Dec. 2023 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 12A (ZELLWEGER); PBD12A](https://omim.org/entry/614886)
[PEROXISOME BIOGENESIS FACTOR 19; PEX19](https://omim.org/entry/600279)
PBD12A 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:614883; 15.08.10]
PBD12A is autosomal recessive and is caused by mutations in the Hsap\PEX19 gene. [from MIM:614883; 15.08.10]
Peroxisomal membrane formation is completely absent in cell lines from individual with mutations in HSap\PEX19 (peroxisome biogenesis disorder 12A). [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.08.10]
The PEX19 gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins [from Gene_cards:PEX19, 2015.08.10]
PBD12A is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. [from MIM:614883; 15.08.10]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene PEX19 (1 Drosophila to 1 human). Dmel\Pex19 shares 30% identity and 50% similarity with human PEX19.
