Tags

Type your tag names separated by a space and hit enter

Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome.
Arch Ophthalmol 2011; 129(1):81-7AO

Abstract

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.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, The University of Iowa, 375 Newton Rd, 4111 MERF, Iowa City, IA 52242, USA. edwin-stone@uiowa.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21220633

Citation

Stone, Edwin M., et al. "Variations in NPHP5 in Patients With Nonsyndromic Leber Congenital Amaurosis and Senior-Loken Syndrome." Archives of Ophthalmology (Chicago, Ill. : 1960), vol. 129, no. 1, 2011, pp. 81-7.
Stone EM, Cideciyan AV, Aleman TS, et al. Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome. Arch Ophthalmol. 2011;129(1):81-7.
Stone, E. M., Cideciyan, A. V., Aleman, T. S., Scheetz, T. E., Sumaroka, A., Ehlinger, M. A., ... Jacobson, S. G. (2011). Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome. Archives of Ophthalmology (Chicago, Ill. : 1960), 129(1), pp. 81-7. doi:10.1001/archophthalmol.2010.330.
Stone EM, et al. Variations in NPHP5 in Patients With Nonsyndromic Leber Congenital Amaurosis and Senior-Loken Syndrome. Arch Ophthalmol. 2011;129(1):81-7. PubMed PMID: 21220633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome. AU - Stone,Edwin M, AU - Cideciyan,Artur V, AU - Aleman,Tomas S, AU - Scheetz,Todd E, AU - Sumaroka,Alexander, AU - Ehlinger,Mary A, AU - Schwartz,Sharon B, AU - Fishman,Gerald A, AU - Traboulsi,Elias I, AU - Lam,Byron L, AU - Fulton,Anne B, AU - Mullins,Robert F, AU - Sheffield,Val C, AU - Jacobson,Samuel G, PY - 2011/1/12/entrez PY - 2011/1/12/pubmed PY - 2011/2/11/medline SP - 81 EP - 7 JF - Archives of ophthalmology (Chicago, Ill. : 1960) JO - Arch. Ophthalmol. VL - 129 IS - 1 N2 - 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. SN - 1538-3601 UR - https://www.unboundmedicine.com/medline/citation/21220633/Variations_in_NPHP5_in_patients_with_nonsyndromic_leber_congenital_amaurosis_and_Senior_Loken_syndrome_ L2 - https://jamanetwork.com/journals/jamaophthalmology/fullarticle/10.1001/archophthalmol.2010.330 DB - PRIME DP - Unbound Medicine ER -