Leber congenital amaurosis: Genes, proteins and disease mechanisms

@article{Hollander2008LeberCA,
  title={Leber congenital amaurosis: Genes, proteins and disease mechanisms},
  author={Anneke I. den Hollander and Ronald Roepman and Robert K Koenekoop and Frans P. M. Cremers},
  journal={Progress in Retinal and Eye Research},
  year={2008},
  volume={27},
  pages={391-419}
}

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References

SHOWING 1-10 OF 304 REFERENCES

Mutational analysis and clinical correlation in Leber congenital amaurosis

Molecular diagnosis of Leber congenital amaurosis could provide important information concerning prognosis and course of treatment, and the clinical presentation was variable; however, the visual evolution in patients with mutations in GUCY2D and CRX remained stable, while individuals with mutationsin the RPE65 gene showed progressive visual loss.

Spectrum of retGC1 mutations in Leber's congenital amaurosis

Screening of the whole coding sequence of the retGC1 gene in 118 patients affected with LCA found 22 different mutations in 24 unrelated families originating from various countries of the world, confirming the previous genotype–phenotype correlations the authors were able to establish.

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

The identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in this series and suggesting that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCAtype I.

Leber congenital amaurosis: Comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype–phenotype correlations as a strategy for molecular diagnosis

A comprehensive mutational analysis of the all known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases, and decisional flowcharts directing the molecular analysis of LCA genes in a given case are drawn.

The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations.

The phenotype of LCA in patients with AIPL1 mutations is relatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset, and the ERG of a parent heterozygote carrier revealed significantly reduced rod function.

Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

Normal retinal thickness and fundus autofluorescence may be the means with which to identify patients with LCA who carry RPE65 mutations, which are expected to be a potential gene therapy target in the near future.

Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles.

The LCAgenotyping microarray is a robust and cost-effective screening tool, representing the prototype of a disease chip for genotyping patients with a genetically heterogeneous condition and allows systematic detection and analysis of genetic variation, facilitating prospective diagnosis and ultimately predicting disease progression.

Mutation screening of 299 Spanish families with retinal dystrophies by Leber congenital amaurosis genotyping microarray.

A mutational analysis of eight genes in 299 unrelated Spanish families, containing 42 patients with initial diagnosis of LCA, found that CRB1 is the main gene responsible for LCA in the Spanish population and changes should be considered as polymorphism or modifier alleles, rather than as disease-causing mutations.

Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis

The LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease and the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA is emphasized.

Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype

It is shown that all patients were affected with the cone‐rod subtype of the disease whatever their NPHP6/CEP290 genotype, and conversely to other LCA genes, N PHP6 is involved in families of European descent only.
...