This report describes visual impairment and progressive phthisis bulbi (degradation of the eye), VIPB, which shows autosomal recessive inheritance. The human gene implicated in this disease is MARK3, which phosphorylates specific microtubule-associated proteins. There is a single high-ranking ortholog of human MARK3 in Drosophila, par-1. Several alleles have been generated for par-1, including those carrying RNAi targeting constructs, tagged constructs, alleles generated by insertional mutagenesis, and hypomorphs. Dmel\par-1 is also orthologous to MARK1, MARK2, and MARK4 in human.
The human gene Hsap\MARK3 has been introduced into flies, but has not been characterized.
Flies expressing a variant of par-1 equivalent to the mutation seen in individuals with VIPB (par-1 p.Arg792Gly) have severely reduced eyes, with a near-complete loss of response in electroretinogram recordings, suggesting that the p.Arg792Gly variant of par-1 acts as a dominant negative mutation. Overexpression of wild-type par-1 causes only very minor eye defects.
[updated Jan. 2020 by FlyBase; FBrf0222196]
[VISUAL IMPAIRMENT AND PROGRESSIVE PHTHISIS BULBI; VIPB](https://omim.org/entry/618283)
[MAP/MICROTUBULE AFFINITY-REGULATING KINASE 3; MARK3](https://omim.org/entry/602678)
In the consanguineous family studied in Ansar et al. 2018 (FBrf0244878), two male individuals developed eye phthisis by adulthood, and one 15-year old female had poor vision with low acuity and hazy cornea. All three were homozygous for the same mutation in MARK3.
Visual impairment and progressive phthisis bulbi is characterized by poor vision at birth, with development of bilateral phthisis by adulthood (Ansar et al. 2018, FBrf0244878). [from MIM:618283, 2020.02.24]
By exome sequencing in a consanguineous Pakistani family in which 3 sibs had visual impairment and progressive phthisis bulbi, Ansar et al. 2018 (FBrf0244878) identified homozygosity for a missense mutation in the MARK3 gene (R570G; 602678.0001) that segregated fully with disease and was found at low frequency in the gnomAD database. [from MIM:618283, 2020.02.24]
Phthisis bulbi denotes end-stage eye disease characterized by shrinkage and disorganization of the eye with the resultant functional loss. The major factors associated with the pathogenesis of phthisis are hypotony, deranged blood-ocular barriers, and inflammation. A phthisical globe shows a small squared off shape, opaque and thickened cornea, thickened sclera, neovascularization of iris, cataract, cyclitic membrane, ciliochoroidal detachment, and retinal detachment. Microscopic features include internal disorganization, inflammatory reaction, a reactive proliferation of various cells, calcification, and ossification. (From Tripathy et al. 2017 and references therein, pubmed:29902388.)
Many to one: 4 human genes to 1 Drosophila gene; multiple less closely related genes in both species.
Moderate- to high-scoring ortholog of human MARK3, MARK1, MARK2, and MARK4; multiple less closely related genes in both species. Dmel\par-1 shares 55% identity and 67% similarity with MARK3.
