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A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration
BACKGROUND: The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826887/ https://www.ncbi.nlm.nih.gov/pubmed/26472407 http://dx.doi.org/10.1136/bjophthalmol-2015-306939 |
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author | Carrigan, Matthew Duignan, Emma Humphries, Pete Palfi, Arpad Kenna, Paul F Farrar, G Jane |
author_facet | Carrigan, Matthew Duignan, Emma Humphries, Pete Palfi, Arpad Kenna, Paul F Farrar, G Jane |
author_sort | Carrigan, Matthew |
collection | PubMed |
description | BACKGROUND: The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa. METHODS: A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies. RESULTS: Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function. CONCLUSION: These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse. |
format | Online Article Text |
id | pubmed-4826887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48268872016-04-19 A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration Carrigan, Matthew Duignan, Emma Humphries, Pete Palfi, Arpad Kenna, Paul F Farrar, G Jane Br J Ophthalmol Clinical Science BACKGROUND: The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa. METHODS: A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies. RESULTS: Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function. CONCLUSION: These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse. BMJ Publishing Group 2016-04 2015-10-15 /pmc/articles/PMC4826887/ /pubmed/26472407 http://dx.doi.org/10.1136/bjophthalmol-2015-306939 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Clinical Science Carrigan, Matthew Duignan, Emma Humphries, Pete Palfi, Arpad Kenna, Paul F Farrar, G Jane A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration |
title | A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration |
title_full | A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration |
title_fullStr | A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration |
title_full_unstemmed | A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration |
title_short | A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration |
title_sort | novel homozygous truncating gnat1 mutation implicated in retinal degeneration |
topic | Clinical Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826887/ https://www.ncbi.nlm.nih.gov/pubmed/26472407 http://dx.doi.org/10.1136/bjophthalmol-2015-306939 |
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