Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia

Abstract

Achromatopsia is an autosomal recessively inherited visual disorder that is present from birth and that features the absence of color discrimination. We here report the identification of five independent families with achromatopsia that segregate protein-truncation mutations in the GNAT2 gene, located on chromosome 1p13. GNAT2 encodes the cone photoreceptor-specific alpha-subunit of transducin, a G-protein of the phototransduction cascade, which couples to the visual pigment(s). Our results demonstrate that GNAT2 is the third gene implicated in achromatopsia.

Figure 1

GNAT2 mutations in families segregating achromatopsia. A and B, Pedigrees of the five achromatopsia families with GNAT2 mutations, including the genotypes of available subjects (denoted by asterisks [*]) as determined by segregation analysis. + = wild type; − = mutation. The geographical origin of the families is indicated by square brackets: I = Italy; DK = Denmark; D = Germany; TK = Turkey. Panel b presents the results of segregation analysis of the exon 4 deletion in family CHRO22. The photograph shows the electrophoretic separation of wild-type alleles (upper band) and mutant alleles (lower band), after amplification by long-distance PCR. M = marker; C = normal control subject. C, Organization of the GNAT2 gene (top) and location of the two repeats (R1 and R2) putatively implicated in the exon 4 deletion (bottom). D, Electropherograms of mutant sequence (bottom) and corresponding wild-type reverse-strand sequence (top), for homozygous mutations c.235C→T (p.Q79X) and c.285_291del7insCTGTAT and for heterozygous mutation c.955delA. Mutation sites are indicated by arrows (↓).