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


METHODS
Retrospective case series.


METHODS
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.


METHODS
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.
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.
Hee Gyung
HG
Kang
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
Yo Han
YH
Ahn
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
Jeong Hun
JH
Kim
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Il-Soo
IS
Ha
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
Young Suk
YS
Yu
Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea.
Yong-Hoon
YH
Park
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Hae Il
HI
Cheong
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D017668:Age of Onset; D002648:Child; D003598:Cytoskeletal Proteins; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005784:Gene Amplification; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics*; D009887:Ophthalmoscopy; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies; D017384:Sequence Deletion; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C110862:MALL protein, human; D008565:Membrane Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; C108725:NPHP1 protein, human
MALL; NPHP1; nephronophthisis; retinopathy