Whole exome sequencing identifies a novel splice-site mutation in IMPG2 gene causing Stargardt-like juvenile macular dystrophy in a north Indian family

Gene. 2022 Mar 30:816:146158. doi: 10.1016/j.gene.2021.146158. Epub 2022 Jan 4.

Abstract

We report on the genetic analysis of a north Indian family affected with Stargardt-like juvenile macular dystrophy. Considering an autosomal recessive inheritance of macular dystrophy in the recruited family, whole exome sequencing was employed in two affected siblings and their mother. We have identified a novel splice-site variant NC_000003.11(NM_016247.3):c.1239 + 1G > T, co-segregating in the affected siblings, in the Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) gene. The identified variant is present immediately after exon 11, and is predicted to disrupt the wild-type donor splice-site of IMPG2 transcripts. We confirmed the splice-site changes in the IMPG2 transcripts using minigene functional assay. Although a number of studies on IMPG2 have demonstrated its involvement in retinitis pigmentosa and vitelliform macular dystrophy, this is the first report of a splice-site variant in IMPG2 that is responsible for Stargardt-like juvenile macular dystrophy.

Keywords: IMPG2 (Interphotoreceptor Matrix Proteoglycan 2); Splice-site variant; Stargardt-like juvenile macular dystrophy; Whole-exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Computational Biology
  • Exome Sequencing
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Mutation
  • Pedigree
  • Proteoglycans / genetics*
  • RNA Splice Sites / genetics*
  • Stargardt Disease / genetics*
  • Young Adult

Substances

  • IMPG2 protein, human
  • Proteoglycans
  • RNA Splice Sites