Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the α subunit of cone transducin (GNAT2)
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OBJECTIVE: To determine the molecular basis for achromatopsia using autozygosity mapping and positional candidate gene analysis. DESIGN AND METHODS: A large consanguineous Pakistani family containing six subjects with autosomal recessive complete achromatopsia was ascertained. After excluding linkage to the two known achromatopsia genes (CNGA3 and CNGB3), a genome wide linkage screen was undertaken. RESULTS: Significant linkage was detected to a 12 cM autozygous segment between markers D1S485 and D1S2881 on chromosome 1p13. Direct sequence analysis of the candidate gene GNAT2 located within this interval identified a frameshift mutation in exon 7 (c842_843insTCAG; M280fsX291) that segregated with the disease. CONCLUSIONS: The GNAT2 gene codes for cone alpha-transducin, the G protein that couples the cone pigments to cGMP-phosphodiesterase in phototransduction. Although cone alpha-transducin has a fundamental role in cone phototransduction, mutations in GNAT2 have not been described previously. Since mutations in the CNGA3 gene may cause a variety of retinal dystrophies (complete and incomplete achromatopsia and progressive cone dystrophy), GNAT2 mutations may also prove to be implicated in other forms of retinal dystrophy with cone dysfunction.
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A mouse with a naturally occurring mutation in cone photoreceptor function loss-3 (cpfl3) is being used as a model for rod monochromism, or achromatopsia, an autosomal recessive disease in which there is a loss of functional retinal cone photoreceptors, resulting in a disease that presents in infancy with horizontal nystagmus, photophobia, color blindness, and poor visual acuity.
“A mouse with a naturally occurring mutation in cone photoreceptor function loss-3 (cpfl3) is being used a model for rod monochromism, or achromatopsia, an autosomal recessive disease in which there is a loss of functional retinal cone photoreceptors, resulting in a disease that presents in infancy with horizontal nystagmus, photophobia, color blindness, and poor visual acuity”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Aligianis et al., 2002
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- Authors
- Aligianis, I. A., Forshew, T., Johnson, S., Michaelides, M., Johnson, C. A., Trembath, R. C., Hunt, D. M., Moore, A. T., & Maher, E. R.
- Affiliations
- Birmingham Women's Hospital (GB)
- University of Birmingham (GB)
- University College London (GB)
- University of Leicester (GB)
- Corresponding author
- Maher, E R
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2002-09
- Volume
- 39
- Issue
- 9
- Pages
- 656-660
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC1735242
- OpenAlex
- W2072897672
- Cited by
- 130
- References
- 37
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Medical Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- achromatopsia, GNAT2, homozygosity mapping, autosomal recessive inheritance, consanguineous family, retinal dystrophy, cone phototransduction
- MeSH terms
- Amino Acid Sequence, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 1, Color Vision Defects, Consanguinity, DNA, DNA Mutational Analysis, Family Health, Female, Humans, Genetic Linkage, Male, Molecular Sequence Data, Pedigree, Transducin, Sequence Homology, Amino Acid, Germ-Line Mutation, Microsatellite Repeats
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