This report describes peroxisome biogenesis disorder 1A (PBD1A), which is a subtype of peroxisome biogenesis disorder (PBD). The human gene implicated in this disease is PEX1, which is a member of the AAA family of adenosine triphosphatases (ATPases) and is essential for the assembly of functional peroxisomes. Mutations in human PEX1 are the most common cause of PBD. There is a single high-scoring fly ortholog, Pex1, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and a classical hypomorphic allele have been generated.
Multiple UAS constructs of the human Hsap\PEX1 gene have been introduced into flies, both wild-type and a variant implicated in human disease. See the 'Disease-Implicated Variants' table, below. Expression of the G843D variant results in decreased viability at larval, pupal, and adult stages. This system has been used to assess the efficacy of a candidate therapeutic drug.
For loss-of-function mutations in the Dmel\Pex1 gene, observed phenotypes include aspects similar to the human disease, including reduced body size, developmental delays, inability to feed, reduced lifespan, structural defects in the nervous system, and inability to assemble functional peroxisomes.
[updated Sep. 2021 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 1A (ZELLWEGER); PBD1A](https://omim.org/entry/214100)
[PEROXISOME BIOGENESIS FACTOR 1; PEX1](https://omim.org/entry/602136)
PBD1A is one of a group of peroxisome biogenesis disorders characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction. In its most severe form, Zellweger syndrome, affected individuals die in the first year. [from MIM:214100; 15.08.10]
Mutations in PEX1, the most common cause of peroxisome biogenesis disorder, are observed in about 68% of affected individuals. They are associated with the full continuum of clinical phenotypes. [from Gene_reviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum, 2015.08.10]
PBD1A is autosomal recessive and is caused by mutations in the Hsap\PEX1 gene. [from MIM:214100; 15.08.10]
PEX1 is a member of the AAA ATPase family; it is cytoplasmic but is often anchored to the peroxisomal membrane. [from Gene_cards:PEX1, 2015.09.09]
PBD1A is is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. [from MIM:214100; 15.08.10]
One to one: 1 human gene to 1 Drosophila gene.
Ortholog of human gene PEX1 (1 Drosophila to 1 human). Dmel\Pex1 shares 29% identity and 47% similarity with human PEX1; additional more distantly related genes in Drosophila.
