This report describes leukodystrophy, hypomyelinating, 5 (HLD5); HLD5 exhibits autosomal recessive inheritance. The human gene implicated in this disease is FAM126A, which encodes a component of the PI4KIIIα complex. There is a single orthologous gene in Drosophila, Hyccin, for which a small number of genetic reagents have been generated including RNAi-targeting constructs and an overexpression constructs. Dmel\Hyccin is also orthologous to the human gene FAM126B.
UAS constructs of both Hsap\FAM126A and Hsap\FAM126B have been introduced into flies. In both cases, heterologous rescue (functional complementation) of the Dmel\Hyccin visual impairment phenotype has been demonstrated.
Glial-specific knockdown of Dmel\Hyccin, effected by RNAi, causes an impairment of visual function. This genotype has been used to demonstrated that Hyccin is required for the expression and stabilization of the PI4KIIIα complex at the plasma membrane and is essential for the enrichment of glia and formation of the axonal sheath in the fly visual system.
[updated Jan. 2022 by FlyBase; FBrf0222196]
Hypomyelinating leukodystrophies constitute a subset of genetic white matter disorders characterized by substantial and permanent deficits in CNS myelin deposition. Most patients with severe hypomyelination present in infancy or early childhood and develop severe neurological deficits; clinical presentation can also be mild with onset of symptoms in adolescence or adulthood (Wolf et al., 2021; pubmed:33324001).
[LEUKODYSTROPHY, HYPOMYELINATING, 5; HLD5](https://omim.org/entry/610532)
[HYCCIN, PI4KA LIPID KINASE COMPLEX, SUBUNIT 1; HYCC1](https://omim.org/entry/610531)
Hypomyelinating leukodystrophy-5 (HLD5), also known as hypomyelination and congenital cataract (HCC) is characterized by congenital cataract, progressive neurologic impairment, and diffuse myelin deficiency as shown by brain magnetic resonance imaging (Zara et al., 2006; pubmed:16951682). [from MIM:610532; 2022.01.16]
Hypomyelinating leukodystrophy-5 (HLD5) is caused by homozygous mutation in the FAM126A gene. [from MIM:610532; 2022.01.16]
FAM126A encodes a component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane; may have a role in the beta-catenin/Lef signaling pathway. [Gene Cards, FAM126A; 2022.01.16]
Many to one: 2 human genes to 1 Drosophila gene.
High-scoring ortholog of FAM126A; moderate-scoring ortholog of FAM126B (1 Drosophila to 2 human).
