title: The Family of Crumbs Genes and Human Disease.
abstract: The family of vertebrate Crumbs proteins, homologous toDrosophilaCrumbs (Crb), share large extracellular domains with epidermal growth factor-like repeats and laminin-globular domains, a single transmembrane domain, and a short intracellular C-terminus containing a single membrane proximal 4.1/ezrin/radixin/moesin-binding domain and PSD-95/Discs large/ZO-1-binding motifs. There are 3 Crb genes in humans - Crumbs homolog-1(CRB1), Crumbs homolog-2(CRB2), and Crumbs homolog-3(CRB3). Bilallelic loss-of-function mutations inCRB1cause visual impairment, with Leber's congenital amaurosis and retinitis pigmentosa, whereasCRB2mutations are associated with raised maternal serum and amniotic fluid alpha feto-protein levels, ventriculomegaly/hydrocephalus, and renal disease, ranging from focal segmental glomerulosclerosis to congenital Finnish nephrosis.CRB3has not yet been associated with human disease. In this review, we summarize the phenotypic findings associated with deleterious sequence variants inCRB1andCRB2. We discuss the mutational spectrum, animal models of loss of function for both genes and speculate on the likely mechanisms of disease.
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, University of California San Francisco, San Francisco, Calif., USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Slavotinek
keywords: CRB1; CRB2; Crumbs proteins