title: New type of mutations in three spanish families with choroideremia.
abstract: OBJECTIVE
  Choroideremia (CHM) is an X-linked ophthalmic disease. The gene associated with CHM (REP-1) encodes a ubiquitously expressed protein that is indispensable for the posttranslational activation of retina-specific Rab protein. Different mutations, including large genomic rearrangements involving the REP-1 gene, are responsible for CHM, but they all cause the protein to be truncated or absent. The authors screened 20 Spanish families with clinical diagnoses of CHM to determine the molecular cause of the disease.
  
  
  METHODS
  First, the authors performed haplotype analyses to determine whether the disease is linked to the REP-1 gene. In families in whom the disease segregated with the CHM locus (n = 14), mutational screening of the REP-1 gene was performed.
  
  
  RESULTS
  In 13 of the 14 families in which the phenotype segregated with the CHM locus, the authors identified the mutation associated with the disease. Eight different molecular defects that led to truncation and one that led to complete absence of the REP-1 protein were found in nine families and one family, respectively. Furthermore, the authors identified a novel type of mutation in the REP-1 gene in three families. This novel type of mutation did not result in a truncated or absent protein. Rather, these patients lost different parts of the REP-1 mRNA in-frame that in all the cases encode a conserved protein domain implicated in the interaction with Rab proteins.
  
  
  CONCLUSIONS
  Based on the different mutations found, the authors propose a four-step protocol for the molecular diagnosis of CHM.
authors.affiliation: Department of Genetics, CIBER-ER, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Hoyos
authors.forename: Isabel
authors.initials: I
authors.lastname: Lorda-Sanchez
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Garre
authors.forename: Cristina
authors.initials: C
authors.lastname: Villaverde
authors.forename: Diego
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: Ana
authors.initials: A
authors.lastname: Bustamante
authors.forename: Dan
authors.initials: D
authors.lastname: Diego-Alvarez
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespin
authors.forename: Jesus
authors.initials: J
authors.lastname: Gallego-Merlo
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Trujillo
authors.forename: Carmen
authors.initials: C
authors.lastname: Ramos
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D015139:Blotting, Southern; D015794:Choroideremia / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D015151:Immunoblotting; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013030:Spain; D044465:White People / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D012333:RNA, Messenger; D020691:rab GTP-Binding Proteins