This report describes peroxisome biogenesis disorder 14B (PBD14B), which is a subtype of peroxisome biogenesis disorder. The human gene implicated in this disease is PEX11B, which encodes a protein that is essential for the assembly of functional peroxisomes. There is a single high-scoring fly ortholog, Pex11ab, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated.
For loss-of-function mutations in the Dmel\Pex11ab gene, as with loss of the human ortholog, mutants exhibit an inability to assemble functional peroxisomes.
[updated Oct. 2015 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 14B; PEX14B](https://omim.org/entry/614920)
[PEROXISOME BIOGENESIS FACTOR 11B; PEX11B](https://omim.org/entry/603867)
PBD14B is characterized clinically by mild intellectual disability, congenital cataracts, progressive hearing loss, and polyneuropathy. Additionally, recurrent migraine-like episodes following mental stress or physical exertion, not a common feature in peroxisome disorders, was reported. [from MIM:614920; 15.09.03]
PBD14B is autosomal recessive and is caused by mutations in the Hsap\PEX11B gene. [from MIM:614920; 15.09.03]
A defect in peroxisomal division is observed and peroxisomes vary in number and shape but all biochemical parameters assayed are normal. [from MIM:614920; 15.09.03]
The protein encoded by the PEX11B gene is found in peroxisomal membranes. It facilitates peroxisomal proliferation and interacts with PEX19. [from Gene_cards:PEX11, 2015.08.10]
Two to one: 2 human to 1 Drosophila; additional orthologous human gene is PEX11A; additional more distantly related gene in human.
Ortholog of human genes PEX11B and PEX11A (1 Drosophila to 2 human); additional more distantly related gene in human. Dmel\Pex11ab shares 32% identity and 52% similarity with human PEX11B and 33% identity and 52% similarity with PEX11A.
