IQCB1 mutations in patients with Leber congenital amaurosis

• Verfasst von: Estrada-Cuzcano, Alejandro [VerfasserIn]
• Verfasst von: Koenekoop, Robert K. [VerfasserIn]
• Verfasst von: Coppieters, Frauke [VerfasserIn]
• Verfasst von: Kohl, Susanne [VerfasserIn]
• Verfasst von: Lopez, Irma [VerfasserIn]
• Verfasst von: Collin, Rob W. J. [VerfasserIn]
• Verfasst von: De Baere, Elfride B. W. [VerfasserIn]
• Verfasst von: Roeleveld, Debbie [VerfasserIn]
• Verfasst von: Marek, Jonah [VerfasserIn]
• Verfasst von: Bernd, Antje [VerfasserIn]
• Verfasst von: Rohrschneider, Klaus [VerfasserIn]
• Verfasst von: van den Born, L. Ingeborgh [VerfasserIn]
• Verfasst von: Meire, Françoise [VerfasserIn]
• Verfasst von: Maumenee, Irene H. [VerfasserIn]
• Verfasst von: Jacobson, Samuel G. [VerfasserIn]
• Verfasst von: Hoyng, Carel B. [VerfasserIn]
• Verfasst von: Zrenner, Eberhart [VerfasserIn]
• Verfasst von: Cremers, Frans P. M. [VerfasserIn]
• Verfasst von: den Hollander, Anneke I. [VerfasserIn]
• Titel: IQCB1 mutations in patients with Leber congenital amaurosis
• Verf.angabe: 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, Françoise Meire, Irene H. Maumenee, Samuel G. Jacobson, Carel B. Hoyng, Eberhart Zrenner, Frans P.M. Cremers, and Anneke I. den Hollander
• E-Jahr: 2011
• Jahr: February 2011
• Umfang: 6 S.
• Fussnoten: Gesehen am 02.05.2022
• Titel Quelle: Enthalten in: Investigative ophthalmology & visual science
• Ort Quelle: Rockville, Md. : ARVO, 1977
• Jahr Quelle: 2011
• Band/Heft Quelle: 52(2011), 2, Seite 834-839
• ISSN Quelle: 1552-5783
• DOI: doi:10.1167/iovs.10-5221
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1800625030

Abstract

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. Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes. 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. 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.