This report describes peroxisome biogenesis disorder 13A (PBD13A), which is a subtype of peroxisome biogenesis disorder. The human gene implicated in this disease is PEX14, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex14, for which RNAi targeting constructs and an insertion allele have been generated.
For loss-of-function mutations in the Dmel\ Pex14 gene, as with loss of the human orthologue, mutants exhibit an inability to assemble functional peroxisomes. Work in Drosophila has implicated a subset of peroxide proteins, including Pex14, in additional roles in regulation of lipid storage. Pex14 appears to play an active role in lipid droplet regulation that is functionally and/or temporally distinct from its role in peroxisome biogenesis or movement.
A Drosophila cell line that carries a knockout mutation in Pex19, S2R+-Pex19-KO-A1 (FBtc0000306), has been used to characterize the role of Pex14 and several other 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 13A (ZELLWEGER); PBD13A](https://omim.org/entry/614887)
[PEROXISOME BIOGENESIS FACTOR 14; PEX14](https://omim.org/entry/601791)
PBD13A is one of a group of peroxisome biogenesis disorders characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. In its most severe form, Zellweger syndrome, affected individuals do not show significant development and die in the first year. [from MIM:614887; 15.09.10]
PBD1A is autosomal recessive and is caused by mutations in the Hsap\PEX14 gene. [from MIM:614887; 15.09.10]
PEX14 encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. [from Gene_cards:PEX14, 2015.09.09]
PBD13A is is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. [from MIM:614887; 15.09.10]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene PEX14 (1 Drosophila to 1 human). Dmel\Pex14 shares 30% identity and 49% similarity with human PEX14.
