TY - JOUR T1 - Mapping of a novel locus for achromatopsia (<em>ACHM4</em>) to 1p and identification of a germline mutation in the α subunit of cone transducin (<em>GNAT2</em>) JF - Journal of Medical Genetics JO - J Med Genet SP - 656 LP - 660 DO - 10.1136/jmg.39.9.656 VL - 39 IS - 9 AU - I A Aligianis AU - T Forshew AU - S Johnson AU - M Michaelides AU - C A Johnson AU - R C Trembath AU - D M Hunt AU - A T Moore AU - E R Maher Y1 - 2002/09/01 UR - http://jmg.bmj.com/content/39/9/656.abstract N2 - 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 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. ER -