Homozygous stop-gain variant in LRRC32, encoding a TGFβ receptor, associated with cleft palate, proliferative retinopathy, and developmental delay

Eur J Hum Genet. 2019 Aug;27(8):1315-1319. doi: 10.1038/s41431-019-0380-y. Epub 2019 Apr 11.

Abstract

The transforming growth factor-beta (TGFβ) signaling pathway is essential for palatogenesis and retinal development. Glycoprotein A repetitions predominant (GARP), encoded by LRRC32, is a TGFβ cell surface receptor that has been studied primarily in the context of cellular immunity. We identified a homozygous stop-gain variant in LRRC32 (c.1630C>T; p.(Arg544Ter)) in two families with developmental delay, cleft palate, and proliferative retinopathy. Garp-null mice have palate defects and die within 24 h after birth. Our study establishes LRRC32 as a candidate disease-associated gene in humans and lends further support to the role of the TGFβ pathway in palatogenesis and retinal development.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Cleft Palate / genetics*
  • Codon, Nonsense*
  • Developmental Disabilities / genetics*
  • Family Health
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Pedigree
  • Receptors, Transforming Growth Factor beta / genetics*
  • Vitreoretinopathy, Proliferative / genetics*

Substances

  • Codon, Nonsense
  • LRRC32 protein, human
  • Membrane Proteins
  • Receptors, Transforming Growth Factor beta