Loss-of-function in IRF2BPL is associated with neurological phenotypes

Abstract

53The

IRF2BPL mutation causes nigrostriatal degeneration presenting with dystonia, spasticity and keratoconus

“…De novo mutations in the interferon regulatory factor 2 binding proteinlike (IRF2BPL) gene have been recently associated with different neurological phenotypes [1,2]. Clinical features include neurodevelopmental regression or speech and motor developmental delay, seizures, hypotonia, coordination difficulties, dystonia and pyramidal signs.…”

“…Common clinical features in IRF2BPL mutation carriers include a variety of neurological symptoms from dystonia, ataxia, spasticity, dysarthria/anarthria, dysphagia and epilepsy to neurodevelopmental delay or regression [1][2][3][4]. We also wish to highlight the association of IRF2BPL mutations with keratoconus.…”

Do variants in IRF2BPL cause both neurological disorders and keratoconus 8?

“…Interestingly, all individuals with a combination of neurological symptomatology and keratoconus or other ophthalmological abnormalities and IRF2BPL variants carried de novo truncating variants (Fig. 1), and it has been noted previously that more severe phenotypes were seen in patients with truncating IRF2BPL variants than in those carrying missense variants [6,11]. The remaining reports of patients with this disease do not mention ophthalmological disease except eye movement abnormalities, but severe neurological symptomatology might have overshadowed eye disease.…”

“…is most often in the first decade of life, although later onset cases have been described. Functional studies have shown that loss-of-function of IRF2BPL, or its homologue in animals, leads to neurodegeneration and is associated with abnormalities in endolysosomal storage [6,10].…”

Recent Developments in Using Drosophila as a Model for Human Genetic Disease

“…Finally, a recent report from the UDN and MOSC has linked loss-of-function truncation mutations in the Interferon Regulatory Factor 2 Binding Protein Like ( IRF2BPL ) gene with a syndrome involving severe neurodevelopmental regression, hypotonia, ataxia, seizures, and lack of coordination [ 42 ]. Null mutations in the Drosophila homologue pits (Protein interacting with Ttk69 and Sin3A) are lethal, while partial knockdown of pits by RNA interference produces neurodegenerative phenotypes.…”