Disruption of P2RY5, an Orphan G Protein-Coupled Receptor, Underlies Autosomal Recessive Woolly Hair

Nat Genet. 2008 Mar;40(3):335-9. doi: 10.1038/ng.100. Epub 2008 Feb 24.

Abstract

The genetic determinants of hair texture in humans are largely unknown. Several human syndromes exist in which woolly hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly hair has only rarely been reported. To identify a gene involved in controlling hair texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2-14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein-coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining hair texture in humans.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosome Disorders / genetics
  • Chromosomes, Human, Pair 13
  • Consanguinity
  • DNA Mutational Analysis
  • Family
  • Genes, Recessive
  • Hair / pathology
  • Hair Diseases / genetics*
  • Hair Diseases / pathology
  • Humans
  • Models, Molecular
  • Mutation, Missense
  • Pedigree
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, Purinergic P2 / genetics*

Substances

  • LPAR4 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Purinergic P2

Associated data

  • RefSeq/NM_005767
  • RefSeq/NP_005758