title: IQCB1 mutations in patients with leber congenital amaurosis.
abstract: OBJECTIVE
  Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA.
  
  
  METHODS
  Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes.
  
  
  RESULTS
  In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal.
  
  
  CONCLUSIONS
  Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Estrada-Cuzcano
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: Frauke
authors.initials: F
authors.lastname: Coppieters
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Elfride B W
authors.initials: EB
authors.lastname: De Baere
authors.forename: Debbie
authors.initials: D
authors.lastname: Roeleveld
authors.forename: Jonah
authors.initials: J
authors.lastname: Marek
authors.forename: Antje
authors.initials: A
authors.lastname: Bernd
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohrschneider
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Françoise
authors.initials: F
authors.lastname: Meire
authors.forename: Irene H
authors.initials: IH
authors.lastname: Maumenee
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000293:Adolescent; D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D000072661:Ciliopathies; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics; D057130:Leber Congenital Amaurosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D002148:Calmodulin-Binding Proteins; D018389:Codon, Nonsense; C498171:IQCB1 protein, human