ARHGAP35 is a novel factor disrupted in human developmental eye phenotypes. Eur J Hum Genet 2023 Mar;31(3):363-367
Date
12/01/2022Pubmed ID
36450800Pubmed Central ID
PMC9995503DOI
10.1038/s41431-022-01246-zScopus ID
2-s2.0-85143135154 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
ARHGAP35 has known roles in cell migration, invasion and division, neuronal morphogenesis, and gene/mRNA regulation; prior studies indicate a role in cancer in humans and in the developing eyes, neural tissue, and renal structures in mice. We identified damaging variants in ARHGAP35 in five individuals from four families affected with anophthalmia, microphthalmia, coloboma and/or anterior segment dysgenesis disorders, together with variable non-ocular phenotypes in some families including renal, neurological, or cardiac anomalies. Three variants affected the extreme C-terminus of the protein, with two resulting in a frameshift and C-terminal extension and the other a missense change in the Rho-GAP domain; the fourth (nonsense) variant affected the middle of the gene and is the only allele predicted to undergo nonsense-mediated decay. This study implicates ARHGAP35 in human developmental eye phenotypes. C-terminal clustering of the identified alleles indicates a possible common mechanism for ocular disease but requires further studies.
Author List
Reis LM, Chassaing N, Bardakjian T, Thompson S, Schneider A, Semina EVAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnophthalmos
Coloboma
Eye Abnormalities
Guanine Nucleotide Exchange Factors
Humans
Mice
Microphthalmos
Mutation
Phenotype
Repressor Proteins
