Unique noncoding variants upstream of PRDM13 are associated with a spectrum of developmental retinal dystrophies including progressive bifocal chorioretinal atrophy

Hum Mutat. 2019 May;40(5):578-587. doi: 10.1002/humu.23715. Epub 2019 Feb 14.


The autosomal dominant progressive bifocal chorioretinal atrophy (PBCRA) disease locus has been mapped to chromosome 6q14-16.2 that overlaps the North Carolina macular dystrophy (NCMD) locus MCDR1. NCMD is a nonprogressive developmental macular dystrophy, in which variants upstream of PRDM13 have been implicated. Whole genome sequencing was performed to interrogate structural variants (SVs) and single nucleotide variants (SNVs) in eight individuals, six affected individuals from two families with PBCRA, and two individuals from an additional family with a related developmental macular dystrophy. A SNV (chr6:100,046,804T>C), located 7.8 kb upstream of the PRDM13 gene, was shared by all PBCRA-affected individuals in the disease locus. Haplotype analysis suggested that the variant arose independently in the two families. The two affected individuals from Family 3 were screened for rare variants in the PBCRA and NCMD loci. This revealed a de novo variant in the proband, 21 bp from the first SNV (chr6:100,046,783A>C). This study expands the noncoding variant spectrum upstream of PRDM13 and suggests altered spatio-temporal expression of PRDM13 as a candidate disease mechanism in the phenotypically distinct but related conditions, NCMD and PBCRA.

Keywords: NCMD; PBCRA; PRDM13; macular development; macular dystrophy; whole genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Adult
  • Computational Biology / methods
  • Corneal Dystrophies, Hereditary / diagnosis*
  • Corneal Dystrophies, Hereditary / genetics*
  • Female
  • Genetic Association Studies / methods
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Multigene Family
  • Pedigree
  • Retinal Dystrophies / diagnosis*
  • Retinal Dystrophies / genetics*
  • Transcription Factors / genetics*
  • Whole Genome Sequencing


  • 5' Untranslated Regions
  • Transcription Factors
  • PRDM13 protein, human
  • Histone-Lysine N-Methyltransferase

Supplementary concepts

  • Chorioretinal atrophy, progressive bifocal