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

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.
Tamar Harel 1,  Ephrat Levy-Lahad 2,  Muhannad Daana 3,  Hadas Mechoulam 4,  Smadar Horowitz-Cederboim 2,  Michal Gur 5,  Vardiella Meiner 5,  Orly Elpeleg 5 6
Affiliations

Affiliations

  • 1 Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel. [email protected].
  • 2 Medical Genetics Institute, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
  • 3 Child Development Centers, Clalit and Maccabi Health Care Services, Jerusalem District, Jerusalem, Israel.
  • 4 Center for Pediatric Ophthalmology, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 5 Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel.
  • 6 Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
PMID: 30976112 DOI: 10.1038/s41431-019-0380-y
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.

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