Next-generation sequencing confirms the implication of SLC24A1 in autosomal-recessive congenital stationary night blindness

Clin Genet. 2016 Jun;89(6):690-9. doi: 10.1111/cge.12746. Epub 2016 Mar 4.

Abstract

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs-electroretinogram (ERG) while patients with a signal transmission defect show a Schubert-Bornschein ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs-ERG and only one family with a disease-causing variant in SLC24A1 have been reported. Whole-exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SLC24A1. Indeed, re-investigation of the clinical data corrected the diagnosis to Riggs-form of CSNB. Targeted next-generation sequencing (NGS) identified compound heterozygous deletions and a homozygous missense variant in SLC24A1 in two other patients, respectively. ERG abnormalities varied in these three cases but all patients had normal visual acuity, no myopia or nystagmus, unlike in Schubert-Bornschein-type of CSNB. This confirms that SLC24A1 defects lead to CSNB and outlines phenotype/genotype correlations in CSNB subtypes. In case of unclear clinical characteristics, NGS techniques are helpful to clarify the diagnosis.

Keywords: SLC24A1; congenital stationary night blindness; high-throughput sequencing; humans.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Electroretinography
  • Exome / genetics
  • Eye Diseases, Hereditary / diagnosis
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / physiopathology
  • Family Health
  • Female
  • Genes, Recessive*
  • Genetic Diseases, X-Linked / diagnosis
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / physiopathology
  • Genetic Predisposition to Disease / genetics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Homozygote
  • Humans
  • Male
  • Mutation*
  • Myopia / diagnosis
  • Myopia / genetics*
  • Myopia / physiopathology
  • Night Blindness / diagnosis
  • Night Blindness / genetics*
  • Night Blindness / physiopathology
  • Pedigree
  • Sequence Homology, Amino Acid
  • Sodium-Calcium Exchanger / genetics*

Substances

  • Sodium-Calcium Exchanger
  • potassium-dependent sodium-calcium exchanger

Supplementary concepts

  • Night blindness, congenital stationary