Archives of ophthalmology (Chicago, Ill. : 1960) · 2011
Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Stone Edwin M, Cideciyan Artur V, Aleman Tomas S, Scheetz Todd E, Sumaroka Alexander, Ehlinger Mary A, Schwartz Sharon B, Fishman Gerald A, Traboulsi Elias I, Lam Byron L, Fulton Anne B, Mullins Robert F, Sheffield Val C, Jacobson Samuel G
Аннотация
OBJECTIVE: To investigate whether mutations in NPHP5 can cause Leber congenital amaurosis (LCA) without early-onset renal disease.
METHODS: DNA samples from 276 individuals with nonsyndromic LCA were screened for variations in the NPHP5 gene. Each had been previously screened for mutations in 8 known LCA genes without identifying a disease-causing genotype.
RESULTS: Nine of the 276 LCA probands (3.2%) harbored 2 plausible disease-causing mutations (7 different alleles) in NPHP5. Four of these have been previously reported in patients with Senior-Loken syndrome (F141del, R461X, H506del, and R489X) and 3 are novel (A111del, E346X, and R455X). All 9 patients had severe visual loss from early childhood but none had overt renal disease in the first decade of life. Two patients were diagnosed with nephronophthisis in the second decade. Retinal imaging studies showed retained photoreceptor nuclei and retinal pigment epithelium integrity mainly in the cone-rich central retina, a phenotype with strong similarities to that of NPHP6 disease.
CONCLUSIONS: Mutations in NPHP5 can cause LCA without early-onset renal disease. Abnormalities observed in the photoreceptor outer segments (a cilial structure) may explain the severe visual loss in NPHP5 -associated LCA. Clinical Relevance The persistence of central photoreceptor nuclei despite severe visual loss in NPHP5 disease is encouraging for future therapeutic interventions.
METHODS: DNA samples from 276 individuals with nonsyndromic LCA were screened for variations in the NPHP5 gene. Each had been previously screened for mutations in 8 known LCA genes without identifying a disease-causing genotype.
RESULTS: Nine of the 276 LCA probands (3.2%) harbored 2 plausible disease-causing mutations (7 different alleles) in NPHP5. Four of these have been previously reported in patients with Senior-Loken syndrome (F141del, R461X, H506del, and R489X) and 3 are novel (A111del, E346X, and R455X). All 9 patients had severe visual loss from early childhood but none had overt renal disease in the first decade of life. Two patients were diagnosed with nephronophthisis in the second decade. Retinal imaging studies showed retained photoreceptor nuclei and retinal pigment epithelium integrity mainly in the cone-rich central retina, a phenotype with strong similarities to that of NPHP6 disease.
CONCLUSIONS: Mutations in NPHP5 can cause LCA without early-onset renal disease. Abnormalities observed in the photoreceptor outer segments (a cilial structure) may explain the severe visual loss in NPHP5 -associated LCA. Clinical Relevance The persistence of central photoreceptor nuclei despite severe visual loss in NPHP5 disease is encouraging for future therapeutic interventions.
Предметные рубрики MeSH
AdolescentCalmodulin-Binding ProteinsChildChild, PreschoolChromosomes, Human, Pair 3CiliopathiesDNA Mutational AnalysisFemaleGenotypeHumansInfantKidney Diseases, CysticLeber Congenital AmaurosisMaleMutationOphthalmoscopyOptic Atrophies, HereditaryPedigreeRetinaTomography, Optical CoherenceVision DisordersYoung Adult