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

Hum Mutat. 2019 Aug;40(8):1145-1155. doi: 10.1002/humu.23768. Epub 2019 May 6.

Abstract

Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing variants, of which 12 are novel, were identified. The mutation spectrum also includes 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 patients carry just a single heterozygous variant. In addition to our previous study on GNAT2-ACHM, we also present detailed clinical data of these patients.

Keywords: GNAT2; achromatopsia; copy number variations; mutations; transducin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Color Vision Defects / genetics*
  • DNA Copy Number Variations
  • Exons
  • Female
  • Genetic Predisposition to Disease
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Sequence Analysis, DNA / methods*
  • Young Adult

Substances

  • Heterotrimeric GTP-Binding Proteins