PMID- 34259982
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 1573-2622 (Electronic)
IS  - 0012-4486 (Linking)
VI  - 143
IP  - 3
DP  - 2021 Dec
TI  - Compound Heterozygous Mutations in ZNF408 in a Patient with a Late Onset 
      Pigmentary Retinopathy and Relatively Preserved Central Retina.
PG  - 305-312
LID - 10.1007/s10633-021-09847-7 [doi]
AB  - PURPOSE: To describe in detail the phenotype of a patient with compound 
      heterozygous mutations in ZNF408 and an adult-onset pigmentary retinopathy rather 
      than familial exudative vitreoretinopathy as expected with heterozygous mutations 
      in this gene. METHODS: A 70-year-old male presented with a pigmentary 
      retinopathy, which prompted a genetic evaluation that revealed two variants in 
      trans in the ZNF408 gene. He underwent an ophthalmic examination, kinetic fields, 
      electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), 
      fundus autofluorescence, wide-angle fluorescein angiography and near-infrared 
      imaging. RESULTS: Visual acuity was 20/20 for both eyes. Fundus examination 
      showed epiretinal membrane, vascular attenuation and peripheral bone spicule 
      pigmentation in both eyes. Fluorescein angiography showed no vascular anomalies 
      in both eyes. Fundus autofluorescence showed a preserved island of fundus 
      autofluorescence centrally. Visual field by kinetic perimetry (V-4e stimulus) 
      showed generalized constriction to 40 degrees of eccentricity and by an I-4e 
      target showed generalized constriction to 10 degrees of eccentricity. ERG showed 
      detectable but reduced cone-mediated responses. SD-OCT demonstrated preserved 
      outer nuclear layer thickness centrally, which decreased with eccentricity. 
      Static perimetry showed substantial rod and cone sensitivities centrally that 
      declined with eccentricity. A next-generation sequencing panel revealed 
      bi-allelic variants (p.Arg567Ter; c.1699C > T and p.Leu566His; c.1697 T > A) in 
      the ZNF408 gene. CONCLUSIONS: ZNF408-associated retinal dystrophies can present 
      with predominantly retinal findings and should be considered in the differential 
      diagnosis of retinitis pigmentosa. Our study revealed a novel variant p.L566H, 
      which to our knowledge has not previously been reported.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Nadelmann, Jennifer B
AU  - Nadelmann JB
AD  - Scheie Eye Institute at the Perelman Center for Advanced Medicine, Department of 
      Ophthalmology, University of Pennsylvania, 3400 Civic Center Boulevard, 
      Philadelphia, PA, 19104, USA.
FAU - O'Neil, Erin C
AU  - O'Neil EC
AD  - Scheie Eye Institute at the Perelman Center for Advanced Medicine, Department of 
      Ophthalmology, University of Pennsylvania, 3400 Civic Center Boulevard, 
      Philadelphia, PA, 19104, USA.
FAU - Kim, Dale S
AU  - Kim DS
AD  - Scheie Eye Institute at the Perelman Center for Advanced Medicine, Department of 
      Ophthalmology, University of Pennsylvania, 3400 Civic Center Boulevard, 
      Philadelphia, PA, 19104, USA.
FAU - Juusola, Jane
AU  - Juusola J
AD  - Clinical Genomics Program, GeneDx, Gaithersburg, MD, USA.
FAU - Aleman, Tomas S
AU  - Aleman TS
AUID- ORCID: 0000-0001-5709-0236
AD  - Scheie Eye Institute at the Perelman Center for Advanced Medicine, Department of 
      Ophthalmology, University of Pennsylvania, 3400 Civic Center Boulevard, 
      Philadelphia, PA, 19104, USA. aleman@pennmedicine.upenn.edu.
AD  - The Center for Advanced Retinal and Ocular Therapeutics, Department of 
      Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA. 
      aleman@pennmedicine.upenn.edu.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210714
PL  - Netherlands
TA  - Doc Ophthalmol
JT  - Documenta ophthalmologica. Advances in ophthalmology
JID - 0370667
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (ZNF408 protein, human)
SB  - IM
MH  - Aged
MH  - DNA-Binding Proteins/genetics
MH  - *Electroretinography
MH  - Fluorescein Angiography
MH  - Humans
MH  - Male
MH  - Mutation
MH  - Retina
MH  - *Retinitis Pigmentosa/diagnosis/genetics
MH  - Tomography, Optical Coherence
MH  - Transcription Factors
OTO - NOTNLM
OT  - ERG
OT  - FEVR
OT  - Familial exudative vitreoretinopathy
OT  - OCT
OT  - Retinitis pigmentosa
OT  - ZNF408
EDAT- 2021/07/15 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/07/14 12:32
PHST- 2021/03/08 00:00 [received]
PHST- 2021/06/24 00:00 [accepted]
PHST- 2021/07/15 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/14 12:32 [entrez]
AID - 10.1007/s10633-021-09847-7 [pii]
AID - 10.1007/s10633-021-09847-7 [doi]
PST - ppublish
SO  - Doc Ophthalmol. 2021 Dec;143(3):305-312. doi: 10.1007/s10633-021-09847-7. Epub 
      2021 Jul 14.