NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy

TY - JOUR

T1 - NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy

AU - Birtel, Johannes

AU - Spital, Georg

AU - Book, Marius

AU - Habbig, Sandra

AU - Bäumner, Sören

AU - Riehmer, Vera

AU - Beck, Bodo B

AU - Rosenkranz, David

AU - Bolz, Hanno J

AU - Dahmer-Heath, Mareike

AU - Herrmann, Philipp

AU - König, Jens

AU - Charbel Issa, Peter

N1 - Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - Biallelic deletions in the NPHP1 gene are the most frequent molecular defect of nephronophthisis, a kidney ciliopathy and leading cause of hereditary end-stage kidney disease. Nephrocystin 1, the gene product of NPHP1, is also expressed in photoreceptors where it plays an important role in intra-flagellar transport between the inner and outer segments. However, the human retinal phenotype has never been investigated in detail. Here, we characterized retinal features of 16 patients with homozygous deletions of the entire NPHP1 gene. Retinal assessment included multimodal imaging (optical coherence tomography, fundus autofluorescence) and visual function testing (visual acuity, full-field electroretinography, color vision, visual field). Fifteen patients had a mild retinal phenotype that predominantly affected cones, but with relative sparing of the fovea. Despite a predominant cone dysfunction, night vision problems were an early symptom in some cases. The consistent retinal phenotype on optical coherence tomography images included reduced reflectivity and often a granular appearance of the ellipsoid zone, fading or loss of the interdigitation zone, and mild outer retinal thinning. However, there were usually no obvious structural changes visible upon clinical examination and fundus autofluorescence imaging (occult retinopathy). More advanced retinal degeneration might occur with ageing. An identified additional CEP290 variant in one patient with a more severe retinal degeneration may indicate a potential role for genetic modifiers, although this requires further investigation. Thus, diagnostic awareness about this distinct retinal phenotype has implications for the differential diagnosis of nephronophthisis and for individual prognosis of visual function.

AB - Biallelic deletions in the NPHP1 gene are the most frequent molecular defect of nephronophthisis, a kidney ciliopathy and leading cause of hereditary end-stage kidney disease. Nephrocystin 1, the gene product of NPHP1, is also expressed in photoreceptors where it plays an important role in intra-flagellar transport between the inner and outer segments. However, the human retinal phenotype has never been investigated in detail. Here, we characterized retinal features of 16 patients with homozygous deletions of the entire NPHP1 gene. Retinal assessment included multimodal imaging (optical coherence tomography, fundus autofluorescence) and visual function testing (visual acuity, full-field electroretinography, color vision, visual field). Fifteen patients had a mild retinal phenotype that predominantly affected cones, but with relative sparing of the fovea. Despite a predominant cone dysfunction, night vision problems were an early symptom in some cases. The consistent retinal phenotype on optical coherence tomography images included reduced reflectivity and often a granular appearance of the ellipsoid zone, fading or loss of the interdigitation zone, and mild outer retinal thinning. However, there were usually no obvious structural changes visible upon clinical examination and fundus autofluorescence imaging (occult retinopathy). More advanced retinal degeneration might occur with ageing. An identified additional CEP290 variant in one patient with a more severe retinal degeneration may indicate a potential role for genetic modifiers, although this requires further investigation. Thus, diagnostic awareness about this distinct retinal phenotype has implications for the differential diagnosis of nephronophthisis and for individual prognosis of visual function.

KW - Adaptor Proteins, Signal Transducing/genetics

KW - Cytoskeletal Proteins/genetics

KW - Electroretinography

KW - Fluorescein Angiography

KW - Humans

KW - Kidney Diseases, Cystic/genetics

KW - Retinal Diseases/genetics

KW - Tomography, Optical Coherence

KW - Visual Fields

U2 - 10.1016/j.kint.2021.06.012

DO - 10.1016/j.kint.2021.06.012

M3 - SCORING: Journal article

C2 - 34153329

VL - 100

SP - 1092

EP - 1100

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 5

ER -