Visual Impairment And Progressive Phthisis Bulbi

A number sign (#) is used with this entry because of evidence that visual impairment and progressive phthisis bulbi (VIPB) is caused by homozygous mutation in the MARK3 gene (602678) on chromosome 14q32. One such family has been reported.

Description

Visual impairment and progressive phthisis bulbi is characterized by poor vision at birth, with development of bilateral phthisis by adulthood (Ansar et al., 2018).

Clinical Features

Ansar et al. (2018) reported a consanguineous Pakistani family (family F105) in which 3 sibs had poor vision at birth. The 2 older affected sibs (V:2 and V:3), who were 30 and 18 years old, developed eye phthisis by adulthood. MRI showed small deformed eye globes bilaterally, with loss of the normal structural differentiation between the anterior and posterior chambers, including the aqueous and vitreous humors. Ultrasonography in patient V:3 showed a thickened posterior wall, vitreous opacity, and small interior-posterior chamber with a 14-mm axial diameter (normal diameter, 24 mm); no posterior eye wall was detected in patient V:2. Their 15-year-old affected sister (V:5) had ptosis with reduced visual acuity and hazy corneas, and examination revealed cornea plana and hypermetropia. Funduscopy was unremarkable.

Molecular Genetics

By exome sequencing in a consanguineous Pakistani family in which 3 sibs had visual impairment and progressive phthisis bulbi, Ansar et al. (2018) 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.

Animal Model

Ansar et al. (2018) generated Drosophila with an R792G mutation in the MARK3 ortholog, Par1, corresponding to the R570G MARK3 mutation identified in patients with VIPB, and observed severely reduced eyes with nearly complete loss of electroretinographic responses.