ARHGEF18 gene

Overview

Gene (OMIM No.)	ARHGEF18 (#616432)
Function of gene/protein	Protein: Rho guanine nucleotide exchange factor 18 Nucleotide exchange factor for Rho GTPases Required for tight junction assembly and barrier formation in epithelial cells Important role in shaping cell morphology
Clinical phenotype (OMIM phenotype no.)	Autosomal recessive retinitis pigmentosa: Retinitis pigmentosa 78 (#617433)
Inheritance	Autosomal recessive
Signs	Shares features with *CRB1*-retinopathy Vessel attenuation Nummular pigment clumping with RPE atrophy Optic disc pallor Cystoid macular oedema may be present Irregular mid-peripheral intraretinal pigment migration
Visual function	Onset in 3rd to 4th decade of life Mild nyctalopia Central visual disturbance Visual field defects BCVA 0.18 to 1.8 logMAR
Systemic features	No extraocular features reported
Key investigations	Full field ERG: rod-cone dystrophy Pattern ERG: subnormal in one patient and undetectable in the other two patients FAF: widespread irregular peripheral hypo-AF OCT: intraretinal cysts; preserved ellipsoid zone (EZ) throughout the macula but this was only retained in the fovea in one patient
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing Whole genome sequencing
Management	Ocular Management of RP
Therapies under research	None at present
Further information	OMIM

Loosli, F. (2013) ArhGEF18regulated Rho signalling in vertebrate retina development. Small GTPases, 4 (4), pg.242–246
Arno, G., Carss, K. J., Hull, S., Zihni, C., Robson, A. G., Fiorentino, A., UK Inherited Retinal Disease Consortium, Hardcastle, A. J., Holder, G. E., Cheetham, M. E., Plagnol, V., NIHR Bioresource-Rare Diseases Consortium, Moore, A. T., Raymond, F. L., Matter, K., Balda, M., Webster, A. R. (2017) Biallelic mutation of ARHGEF18, involved in the determination of epithelial apicobasal polarity, causes adult-onset retinal degeneration. Am. J. Hum. Genet. 100: pg.334-342

Updated on November 30, 2020