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Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 2002 Sep;39(9):656–660. doi: 10.1136/jmg.39.9.656

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

I Aligianis 1, T Forshew 1, S Johnson 1, M Michaelides 1, C Johnson 1, R Trembath 1, D Hunt 1, A Moore 1, E Maher 1
PMCID: PMC1735242  PMID: 12205108

Abstract

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 α-transducin, the G protein that couples the cone pigments to cGMP-phosphodiesterase in phototransduction. Although cone α-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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