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J Med Genet. 2002 Sep;39(9):656-60.

Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the alpha subunit of cone transducin (GNAT2).

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1
Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Abstract

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.

PMID:
12205108
PMCID:
PMC1735242
[Indexed for MEDLINE]
Free PMC Article
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