| http://purl.uniprot.org/citations/29198720 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29198720 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29198720 | http://www.w3.org/2000/01/rdf-schema#comment | "Leber congenital amaurosis (LCA) is a neurodegenerative disease of photoreceptor cells that causes blindness within the first year of life. It occasionally occurs in syndromic metabolic diseases and plurisystemic ciliopathies. Using exome sequencing in a multiplex family and three simplex case subjects with an atypical association of LCA with early-onset hearing loss, we identified two heterozygous mutations affecting Arg391 in β-tubulin 4B isotype-encoding (TUBB4B). Inspection of the atomic structure of the microtubule (MT) protofilament reveals that the β-tubulin Arg391 residue contributes to a binding pocket that interacts with α-tubulin contained in the longitudinally adjacent αβ-heterodimer, consistent with a role in maintaining MT stability. Functional analysis in cultured cells overexpressing FLAG-tagged wild-type or mutant TUBB4B as well as in primary skin-derived fibroblasts showed that the mutant TUBB4B is able to fold, form αβ-heterodimers, and co-assemble into the endogenous MT lattice. However, the dynamics of growing MTs were consistently altered, showing that the mutations have a significant dampening impact on normal MT growth. Our findings provide a link between sensorineural disease and anomalies in MT behavior and describe a syndromic LCA unrelated to ciliary dysfunction."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2017.10.010"xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2017.10.010"xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Cowan N.J."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Cowan N.J."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Tian G."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Tian G."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Lyonnet S."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Lyonnet S."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Kaplan J."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Kaplan J."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Perrault I."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Perrault I."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Paul A."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Paul A."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Boddaert N."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Boddaert N."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Gerard X."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Gerard X."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Rozet J.M."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Rozet J.M."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Bessieres B."xsd:string |
| http://purl.uniprot.org/citations/29198720 | http://purl.uniprot.org/core/author | "Bessieres B."xsd:string |