Achromatopsia (ACHM) Panel

Achromatopsia (ACHM) is a congenital, autosomal recessive retinal disorder characterized by total color blindness, decreased visual acuity (lower than 20/200), photophobia , nystagmus, and absence of cone-mediated electroretinographic amplitudes at birth or early infancy (Kohl et al. 2005. PubMed ID: 15657609; Kohl et al. 2015. PubMed ID: 26029869; Pang et al. 2010. PubMed ID: 20238068). Estimated prevalence is 1/30,000 (Kohl et al. 2002. PubMed ID: 12077706).

With the advent of gene therapy and other types of treatments, the identification of causative genes and variants is becoming increasingly important.

Please see the links for clinical trials and management options below:

Management

ACHM Clinical trials

ACHM is a heterogeneous disorder. Pathogenic variants in CNGA3, CNGB3, GNAT2, PDE6C, PDE6H and ATF6 have been reported to be causative for autosomal recessive ACHM (Ouechtati et al. 2011. PubMed ID: 21107338; Greenberg et al. 2014. PubMed ID: 24504161; Ansar et al. 2015. PubMed ID: 26063662). CNGA3 and CNGB3 are the major causative genes for ACHM, and account for 20-30% and 40-50% of the cases, respectively (Kohl et al. 2005. PubMed ID: 15657609; Wissinger et al. 2001. PubMed ID: 11536077). A frameshift protein truncating variant in CNGB3 (c.1148del, p.Thr383Ilefs*13) has been reported as a predominant pathogenic variant (Kohl et al. 2005. PubMed ID: 15657609; Nishiguchi et al. 2005. PubMed ID: 15712225; Wiszniewski et al. 2007. PubMed ID: 17265047). This variant has been reported at a frequency of 0.2% in general population (gnomAD).A large deletion has been reported only in GNAT2 so far (Kohl et al. 2002. PubMed ID: 12077706; Human Gene Mutation Database). To our knowledge, de novo variants have not been documented causative in the genes associated with ACHM (HGMD-Human Gene Mutation Database).

The proteins encoded by the genes in this panel form the functional cGMP-gated cation channel that is essential for the phototransduction cascade in photoreceptors (Nishiguchi et al. 2005. PubMed ID: 15712225).

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Please see the following table for information regarding clinical sensitivity (Thiadens et al. 2009. PubMed ID: 19615668; Wissinger et al. 2001. PubMed ID: 11536077; Kohl et al. 2002. PubMed ID: 12077706; Kohl et al. 2005. PubMed ID: 15657609; Kohl et al. 2012. PubMed ID: 22901948; Kohl et al. 2015. PubMed ID: 20301591).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).