Atypical retinopathy in patients with nephronophthisis type 1: an uncommon ophthalmological finding

Clin Exp Ophthalmol. 2015 Jul;43(5):437-42. doi: 10.1111/ceo.12469. Epub 2015 Jan 14.

Abstract

Background: Progressive retinal degeneration without retinal pigmentation has been repeatedly observed in Korean nephronophthisis (NPHP) type 1 patients with a total homozygous deletion of NPHP1.

Design: Retrospective case series.

Participants: Patients with clinical diagnosis of NPHP and genetic diagnosis of total deletion of NPHP1 (n = 5) were included in this study.

Methods: Patients with clinical diagnosis of NPHP (n = 57) were screened for total deletion of NPHP1 by polymerase chain reaction (PCR) for the 20 exons of NPHP1. The clinical and ophthalmological findings of NPHP type 1 patients were reviewed. Additionally, four exons of MALL, a gene adjacent to NPHP1, were amplified using PCR, and amplification failure was considered a homozygous deletion encompassing the corresponding exons.

Main outcome measure: Ophthalmological findings in NPHP type 1 patients.

Results: Five of 57 patients with clinical diagnosis of NPHP were diagnosed as having NPHP type 1 by genetic analysis. Chronic renal failure was diagnosed in these five patients at 7.9-15.4 years of age. All the patients with NPHP type 1 had progressive decline in visual acuity with various ages of onset (2-17 years). Ophthalmological examinations revealed unexpected findings of retinopathy with large or small flecks, which was compatible with Stargardt-like retinopathy or albipunctatus retinopathy in majority of them (four of five). The genetic study revealed an additional deletion of exon 1 of the adjacent gene MALL.

Conclusions: We report the unexpectedly common retinal involvement of NPHP type 1 with an additional MALL deletion in a Korean cohort.

Keywords: MALL; NPHP1; nephronophthisis; retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Age of Onset
  • Child
  • Cytoskeletal Proteins
  • Electroretinography
  • Exons / genetics
  • Female
  • Fluorescein Angiography
  • Gene Amplification
  • Humans
  • Kidney Diseases, Cystic / congenital*
  • Kidney Diseases, Cystic / diagnosis
  • Kidney Diseases, Cystic / genetics
  • Male
  • Membrane Proteins / genetics*
  • Myelin and Lymphocyte-Associated Proteolipid Proteins / genetics*
  • Ophthalmoscopy
  • Polymerase Chain Reaction
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / genetics*
  • Retrospective Studies
  • Sequence Deletion
  • Tomography, Optical Coherence
  • Vision Disorders / diagnosis
  • Vision Disorders / genetics
  • Visual Acuity / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • MALL protein, human
  • Membrane Proteins
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • NPHP1 protein, human

Supplementary concepts

  • Nephronophthisis, familial juvenile