Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene

Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by theinability to discriminate colors, nystagmus, photophobia, and low‐visual acuity. Six geneshave been associated with this rare autosomal recessively inherited disease, including theGNAT2 gene encoding the catalytic α‐subunit of the G‐protein transducin which isexpressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independentfamilies diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patientswith ACHM from 19 independent families with likely causative mutations in GNAT2,representing 1.7% of our large ACHM cohort. In total 22 different potentially diseasecausingvariants, of which 12 are novel, were identified. The mutation spectrum alsoincludes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. Two patientscarry just a single heterozygous variant. In addition to our previous study on GNAT2‐ACHM, we also present detailed clinical data of these patients.