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

Irene Aligianis, T Forshew, S Johnson, M Michaelides, Colin Johnson, RC Trembath, DM Hunt, AT Moore, Eamonn Maher

Research output: Contribution to journalArticle

89 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)656-660
Number of pages5
JournalJournal of Medical Genetics
Volume39
Issue number9
DOIs
Publication statusPublished - 1 Sep 2002

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