Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome

Edwin M Stone; Artur V Cideciyan; Tomas S Aleman; Todd E Scheetz; Alexander Sumaroka; Mary A Ehlinger; Sharon B Schwartz; Gerald A Fishman; Elias I Traboulsi; Byron L Lam; Anne B Fulton; Robert F Mullins; Val C Sheffield; Samuel G Jacobson

doi:10.1001/archophthalmol.2010.330

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Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome

Journal article

Open access

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Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome

Edwin M Stone, Artur V Cideciyan, Tomas S Aleman, Todd E Scheetz, Alexander Sumaroka, Mary A Ehlinger, Sharon B Schwartz, Gerald A Fishman, Elias I Traboulsi, Byron L Lam, …

Archives of ophthalmology (1960), Vol.129(1), pp.81-87

01/2011

DOI: 10.1001/archophthalmol.2010.330

PMCID: PMC3952880

PMID: 21220633

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Abstract

To investigate whether mutations in NPHP5 can cause Leber congenital amaurosis (LCA) without early-onset renal disease. 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. 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. 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.

Kidney Diseases, Cystic - diagnosis

Optic Atrophies, Hereditary - genetics

Humans

Child, Preschool

Ciliopathies

Infant

Male

Young Adult

DNA Mutational Analysis

Kidney Diseases, Cystic - genetics

Female

Optic Atrophies, Hereditary - diagnosis

Child

Calmodulin-Binding Proteins - genetics

Tomography, Optical Coherence

Ophthalmoscopy

Genotype

Leber Congenital Amaurosis - genetics

Vision Disorders - diagnosis

Vision Disorders - genetics

Pedigree

Adolescent

Leber Congenital Amaurosis - diagnosis

Mutation

Retina - pathology

Chromosomes, Human, Pair 3 - genetics

Details

Title: Subtitle: Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome
Creators: Edwin M Stone - Department of Ophthalmology and Visual Sciences, The University of Iowa, 375 Newton Rd, 4111 MERF, Iowa City, IA 52242, USA. edwin-stone@uiowa.edu
Artur V Cideciyan
Tomas S Aleman
Todd E Scheetz
Alexander Sumaroka
Mary A Ehlinger
Sharon B Schwartz
Gerald A Fishman
Elias I Traboulsi
Byron L Lam
Anne B Fulton
Robert F Mullins
Val C Sheffield
Samuel G Jacobson
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.129(1), pp.81-87
DOI: 10.1001/archophthalmol.2010.330
PMID: 21220633
PMCID: PMC3952880
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: R01 EY011298 / NEI NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS
Language: English
Date published: 01/2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980083302771

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