Submicroscopic deletions at 13q32.1 cause congenital microcoria

Am J Hum Genet. 2015 Apr 2;96(4):631-9. doi: 10.1016/j.ajhg.2015.01.014. Epub 2015 Mar 12.

Abstract

Congenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 13 / genetics*
  • Comparative Genomic Hybridization
  • Gene Components
  • Genes, Dominant / genetics
  • Humans
  • Hydro-Lyases / genetics
  • Molecular Sequence Data
  • Mutation / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pedigree
  • Pupil Disorders / congenital*
  • Pupil Disorders / genetics
  • Pupil Disorders / pathology
  • Receptors, Cell Surface / genetics*
  • Receptors, G-Protein-Coupled
  • Sequence Analysis, DNA

Substances

  • ITR protein, human
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Hydro-Lyases

Supplementary concepts

  • Microcoria, congenital