This report describes peroxisome biogenesis disorder 6A (PBD6A), which is a subtype of peroxisome biogenesis disorder. The human gene implicated in this disease is PEX10, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex10, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
A UAS construct of a wild-type human Hsap\PEX10 gene has been introduced into flies, but has not been characterized.
For loss-of-function mutations in the Dmel\Pex10 gene, observed phenotypes include aspects similar to the human disease, including elevated very long chain fatty acid (VLCFA) levels, growth defects, and a failure to assemble functional peroxisomes.
[updated Sep. 2018 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 6A (ZELLWEGER); PBD6A](https://omim.org/entry/614870)
[PEROXISOME BIOGENESIS FACTOR 10; PEX10](https://omim.org/entry/602859)
PBD6A 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:614866; 15.08.10]
PBD6A is autosomal recessive and is caused by mutations in the Hsap\PEX10 gene. [from MIM:614866; 15.08.10]
Peroxisomes are missing in skin fibroblasts. [from MIM:614866; 15.08.10]
Pex10 encodes a peroxisomal membrane protein which is involved in the import of peroxisomal matrix proteins. [from Gene_cards:PEX10, 2015.09.09]
PBD6A is is one of a group of peroxisome biogenesis disorders resulting from disordered peroxisome biogenesis. Very long chain fatty acids (VLCFA) were found in the serum of a patient; three peroxisomal beta-oxidation enzymes were missing in liver homogenates. [from MIM:614866; 15.08.10]
One to one: 1 human to 1 Drosophila; additional more distantly related gene(s) in Drosophila.
Ortholog of human gene PEX10 (1 Drosophila to 1 human). Dmel\Pex10 shares 30% identity and 46% similarity with human PEX10; additional more distantly related genes in both species.
