PMID- 32821486
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 2164-2591 (Print)
IS  - 2164-2591 (Electronic)
IS  - 2164-2591 (Linking)
VI  - 9
IP  - 5
DP  - 2020 Apr
TI  - Disease Progression in Patients with Autosomal Dominant Retinitis Pigmentosa due 
      to a Mutation in Inosine Monophosphate Dehydrogenase 1 (IMPDH1).
PG  - 14
LID - 10.1167/tvst.9.5.14 [doi]
LID - 14
AB  - PURPOSE: Mutations in the inosine monophosphate dehydrogenase 1 (IMPDH1) gene are 
      a common cause of inherited retinal degeneration (IRD). Due to species- and 
      tissue-dependent expression of IMPDH1, there are no appropriate models of human 
      IMPDH1 disease. Therefore, a limited understanding remains of disease expression 
      and rates of progression for IMPDH1-related IRD. METHODS: We evaluated 
      semiautomated kinetic and chromatic static perimetry, spectral-domain optical 
      coherence tomography (SD-OCT), and ultra-wide field fundus images with 
      autofluorescence in a cohort of 12 patients (ages 11-58 at first visit). Ten 
      patients had longitudinal data for which rates of progression were estimated. 
      RESULTS: Visual acuities were relatively stable over time and the photoreceptors 
      within the central retina remained intact. Perifoveal photoreceptor loss measured 
      over a period of years coincided with visual fields, which were constricted and 
      progressed over time in all patients. Rod sensitivity showed a similar pattern of 
      defect to that of the kinetic perimetry and the autofluorescence ultra-wide field 
      imaging. Full-field electroretinograms were severely reduced and the dark-adapted 
      rod and mixed responses were extinguished at earlier visits than the 
      light-adapted cone responses. CONCLUSIONS: There was variability in disease 
      severity at the first visit, but results show that the peripheral retina is more 
      susceptible to the deleterious consequences of an IMPDH1 mutation. Given the 
      pattern of degeneration and the alternatively spliced isoforms of IMPDH1, 
      potential interventions may consider targeting the periphery early in disease, 
      modulating transcript expression, and/or preserving central vision at late stages 
      of the disease. TRANSLATIONAL RELEVANCE: These results inform clinical prognosis 
      and offer evidence strategies toward therapeutic intervention.
CI  - Copyright 2020 The Authors.
FAU - Bennett, Lea D
AU  - Bennett LD
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA.
FAU - Klein, Martin
AU  - Klein M
AD  - Retina Foundation of the Southwest, Dallas, TX, USA.
FAU - John, Finny T
AU  - John FT
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA.
FAU - Radojevic, Bojana
AU  - Radojevic B
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, OK, USA.
FAU - Jones, Kaylie
AU  - Jones K
AD  - Retina Foundation of the Southwest, Dallas, TX, USA.
FAU - Birch, David G
AU  - Birch DG
AD  - Retina Foundation of the Southwest, Dallas, TX, USA.
AD  - Department of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.
LA  - eng
GR  - U54 GM104938/GM/NIGMS NIH HHS/United States
GR  - R01 EY009076/EY/NEI NIH HHS/United States
GR  - L30 EY029523/EY/NEI NIH HHS/United States
GR  - R00 EY027460/EY/NEI NIH HHS/United States
GR  - K99 EY027460/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200423
PL  - United States
TA  - Transl Vis Sci Technol
JT  - Translational vision science & technology
JID - 101595919
RN  - 131-99-7 (Inosine Monophosphate)
RN  - EC 1.1.1.205 (IMP Dehydrogenase)
RN  - EC 1.1.1.205 (IMPDH1 protein, human)
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Disease Progression
MH  - Electroretinography
MH  - Humans
MH  - IMP Dehydrogenase/genetics
MH  - *Inosine Monophosphate
MH  - Middle Aged
MH  - Mutation
MH  - *Retinitis Pigmentosa/diagnosis
MH  - Young Adult
PMC - PMC7401855
OTO - NOTNLM
OT  - IMPDH1
OT  - adRP
OT  - clinical outcomes
OT  - disease progression
COIS- Disclosure: L.D. Bennett, None; M. Klein, None; F.T. John, None; B. Radojevic, 
      None; K. Jones, None; D.G. Birch, None
EDAT- 2020/08/22 06:00
MHDA- 2020/08/22 06:01
PMCR- 2020/04/23
CRDT- 2020/08/22 06:00
PHST- 2019/12/09 00:00 [received]
PHST- 2020/02/10 00:00 [accepted]
PHST- 2020/08/22 06:00 [entrez]
PHST- 2020/08/22 06:00 [pubmed]
PHST- 2020/08/22 06:01 [medline]
PHST- 2020/04/23 00:00 [pmc-release]
AID - TVST-19-2175 [pii]
AID - 10.1167/tvst.9.5.14 [doi]
PST - epublish
SO  - Transl Vis Sci Technol. 2020 Apr 23;9(5):14. doi: 10.1167/tvst.9.5.14. 
      eCollection 2020 Apr.