Investigative ophthalmology & visual science · 2011
IQCB1 mutations in patients with leber congenital amaurosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, van den Born L Ingeborgh, Meire Françoise, Maumenee Irene H, Jacobson Samuel G, Hoyng Carel B, Zrenner Eberhart, Cremers Frans P M, den Hollander Anneke I
Аннотация
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'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.
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.
Предметные рубрики MeSH
AdolescentAdultCalmodulin-Binding ProteinsChildChild, PreschoolChromosomes, Human, Pair 3CiliopathiesCodon, NonsenseDNA Mutational AnalysisFemaleFrameshift MutationGenotypeHumansKidney Diseases, CysticLeber Congenital AmaurosisMaleMiddle AgedOptic Atrophies, HereditaryPolymerase Chain ReactionPolymorphism, Single Nucleotide