IQCB1 mutations in patients with leber congenital amaurosis

Alejandro Estrada-Cuzcano, Robert K. Koenekoop, Frauke Coppieters, Susanne Kohl, Irma Lopez, Rob W J Collin, Elfride B W de Baere, Debbie Roeleveld, Jonah Marek, Antje Bernd, Klaus Rohrschneider, L. Ingeborgh van den Born, Fraņcoise Meire, Irene H. Maumenee, Samuel G. Jacobson, Carel B. Hoyng, Eberhart Zrenner, Frans P M Cremers, Anneke I. den Hollander

Research output: Contribution to journalArticle

Abstract

Purpose. 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'sdisease 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.

Original languageEnglish (US)
Pages (from-to)834-839
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Leber Congenital Amaurosis
Mutation
Genes
Renal Insufficiency
Retinal Degeneration
Frameshift Mutation
Chromosomes, Human, Pair 3
Nonsense Codon
Kidney Diseases
Sudden Death
Electrolytes
Single Nucleotide Polymorphism
Cause of Death

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Estrada-Cuzcano, A., Koenekoop, R. K., Coppieters, F., Kohl, S., Lopez, I., Collin, R. W. J., ... den Hollander, A. I. (2011). IQCB1 mutations in patients with leber congenital amaurosis. Investigative Ophthalmology and Visual Science, 52(2), 834-839. https://doi.org/10.1167/iovs.10-5221

IQCB1 mutations in patients with leber congenital amaurosis. / Estrada-Cuzcano, Alejandro; Koenekoop, Robert K.; Coppieters, Frauke; Kohl, Susanne; Lopez, Irma; Collin, Rob W J; de Baere, Elfride B W; Roeleveld, Debbie; Marek, Jonah; Bernd, Antje; Rohrschneider, Klaus; Ingeborgh van den Born, L.; Meire, Fraņcoise; Maumenee, Irene H.; Jacobson, Samuel G.; Hoyng, Carel B.; Zrenner, Eberhart; Cremers, Frans P M; den Hollander, Anneke I.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 2, 02.2011, p. 834-839.

Research output: Contribution to journalArticle

Estrada-Cuzcano, A, Koenekoop, RK, Coppieters, F, Kohl, S, Lopez, I, Collin, RWJ, de Baere, EBW, Roeleveld, D, Marek, J, Bernd, A, Rohrschneider, K, Ingeborgh van den Born, L, Meire, F, Maumenee, IH, Jacobson, SG, Hoyng, CB, Zrenner, E, Cremers, FPM & den Hollander, AI 2011, 'IQCB1 mutations in patients with leber congenital amaurosis', Investigative Ophthalmology and Visual Science, vol. 52, no. 2, pp. 834-839. https://doi.org/10.1167/iovs.10-5221
Estrada-Cuzcano A, Koenekoop RK, Coppieters F, Kohl S, Lopez I, Collin RWJ et al. IQCB1 mutations in patients with leber congenital amaurosis. Investigative Ophthalmology and Visual Science. 2011 Feb;52(2):834-839. https://doi.org/10.1167/iovs.10-5221
Estrada-Cuzcano, Alejandro ; Koenekoop, Robert K. ; Coppieters, Frauke ; Kohl, Susanne ; Lopez, Irma ; Collin, Rob W J ; de Baere, Elfride B W ; Roeleveld, Debbie ; Marek, Jonah ; Bernd, Antje ; Rohrschneider, Klaus ; Ingeborgh van den Born, L. ; Meire, Fraņcoise ; Maumenee, Irene H. ; Jacobson, Samuel G. ; Hoyng, Carel B. ; Zrenner, Eberhart ; Cremers, Frans P M ; den Hollander, Anneke I. / IQCB1 mutations in patients with leber congenital amaurosis. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 2. pp. 834-839.
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AU - Kohl, Susanne

AU - Lopez, Irma

AU - Collin, Rob W J

AU - de Baere, Elfride B W

AU - Roeleveld, Debbie

AU - Marek, Jonah

AU - Bernd, Antje

AU - Rohrschneider, Klaus

AU - Ingeborgh van den Born, L.

AU - Meire, Fraņcoise

AU - Maumenee, Irene H.

AU - Jacobson, Samuel G.

AU - Hoyng, Carel B.

AU - Zrenner, Eberhart

AU - Cremers, Frans P M

AU - den Hollander, Anneke I.

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