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Increased Plasma cGMP in a Family With Autosomal Recessive Retinitis Pigmentosa Due to Homozygous Mutations in the PDE6A Gene

Kjellström, Ulrika LU ; Veiga-Crespo, Patricia LU ; Andréasson, Sten LU and Ekström, Per LU (2016) In Investigative Ophthalmology and Visual Science 57(14). p.6048-6057
Abstract

Purpose: To describe genotype and phenotype in a family with autosomal recessive retinitis pigmentosa (arRP) carrying homozygous mutations in the gene for the α-subunit of cyclic guanosine monophosphate (cGMP)-hydrolyzing phosphodiesterase 6 (PDE6A). Moreover, to compare their plasma cGMP levels to controls, exploring the possible role for cGMP in RP diagnostics.

Methods: Seven siblings and their parents were recruited. Microarray, verified by Sanger sequencing, was used for genotyping. Investigations included slit lamp and fundus examination, Goldmann perimetry, full-field and multifocal electroretinography (ERG), and optical coherence tomography (OCT). Cyclic GMP was measured with an immunoassay kit.

Results: All siblings... (More)

Purpose: To describe genotype and phenotype in a family with autosomal recessive retinitis pigmentosa (arRP) carrying homozygous mutations in the gene for the α-subunit of cyclic guanosine monophosphate (cGMP)-hydrolyzing phosphodiesterase 6 (PDE6A). Moreover, to compare their plasma cGMP levels to controls, exploring the possible role for cGMP in RP diagnostics.

Methods: Seven siblings and their parents were recruited. Microarray, verified by Sanger sequencing, was used for genotyping. Investigations included slit lamp and fundus examination, Goldmann perimetry, full-field and multifocal electroretinography (ERG), and optical coherence tomography (OCT). Cyclic GMP was measured with an immunoassay kit.

Results: All siblings and their father were homozygous, and the mother heterozygous, for IVS6+1G>A in PDE6A. Seven family members also carried c1532G>A in ABCA4. Visual fields were constricted with mere central remnants in older subjects and additional temporal crescents in younger subjects. Visual acuity ranged from 0.8 to amaurosis. Full-field ERGs showed extinguished rod responses and minimal cone responses. Multifocal ERGs were severely reduced. Optical coherence tomography revealed either general attenuation or central macular edema. Mean plasma cGMP in patients was approximately twice that in controls.

Conclusions: To our knowledge, this is the first phenotypic description of arRP due to homozygous IVS6+1G>A mutations in PDE6A and these seem here to be associated with severe RP leading to early extinction of rod responses as well as reduced macular function. Additionally, patients showed increased plasma levels of cGMP, indicating a possible role for cGMP measurements as part of the clinical tests for this and, after further investigations, maybe other forms of RP.

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Contribution to journal
publication status
published
subject
in
Investigative Ophthalmology and Visual Science
volume
57
issue
14
pages
10 pages
publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
external identifiers
  • scopus:84994776874
  • wos:000392380000026
ISSN
1552-5783
DOI
10.1167/iovs.16-19861
language
English
LU publication?
yes
id
c932f7af-f4c5-4c2e-8ed1-94b990d7676f
date added to LUP
2016-11-11 11:12:48
date last changed
2017-11-14 09:52:14
@article{c932f7af-f4c5-4c2e-8ed1-94b990d7676f,
  abstract     = {<p>Purpose: To describe genotype and phenotype in a family with autosomal recessive retinitis pigmentosa (arRP) carrying homozygous mutations in the gene for the α-subunit of cyclic guanosine monophosphate (cGMP)-hydrolyzing phosphodiesterase 6 (PDE6A). Moreover, to compare their plasma cGMP levels to controls, exploring the possible role for cGMP in RP diagnostics.</p><p>Methods: Seven siblings and their parents were recruited. Microarray, verified by Sanger sequencing, was used for genotyping. Investigations included slit lamp and fundus examination, Goldmann perimetry, full-field and multifocal electroretinography (ERG), and optical coherence tomography (OCT). Cyclic GMP was measured with an immunoassay kit.</p><p>Results: All siblings and their father were homozygous, and the mother heterozygous, for IVS6+1G&gt;A in PDE6A. Seven family members also carried c1532G&gt;A in ABCA4. Visual fields were constricted with mere central remnants in older subjects and additional temporal crescents in younger subjects. Visual acuity ranged from 0.8 to amaurosis. Full-field ERGs showed extinguished rod responses and minimal cone responses. Multifocal ERGs were severely reduced. Optical coherence tomography revealed either general attenuation or central macular edema. Mean plasma cGMP in patients was approximately twice that in controls.</p><p>Conclusions: To our knowledge, this is the first phenotypic description of arRP due to homozygous IVS6+1G&gt;A mutations in PDE6A and these seem here to be associated with severe RP leading to early extinction of rod responses as well as reduced macular function. Additionally, patients showed increased plasma levels of cGMP, indicating a possible role for cGMP measurements as part of the clinical tests for this and, after further investigations, maybe other forms of RP.</p>},
  author       = {Kjellström, Ulrika and Veiga-Crespo, Patricia and Andréasson, Sten and Ekström, Per},
  issn         = {1552-5783},
  language     = {eng},
  month        = {11},
  number       = {14},
  pages        = {6048--6057},
  publisher    = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
  series       = {Investigative Ophthalmology and Visual Science},
  title        = {Increased Plasma cGMP in a Family With Autosomal Recessive Retinitis Pigmentosa Due to Homozygous Mutations in the PDE6A Gene},
  url          = {http://dx.doi.org/10.1167/iovs.16-19861},
  volume       = {57},
  year         = {2016},
}