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Disruption of P2RY5, an orphan G protein–coupled receptor, underlies autosomal recessive woolly hair


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 reported1,2. 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.

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Figure 1: Phenotype and fine mapping of ARWH on chromosome 13q14.2–14.3.
Figure 2: Identification of mutations in P2RY5.
Figure 3: Structure of P2RY5 and positions of the mutations.
Figure 4: P2RY5 expression in the human hair follicle.

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We are grateful to the family members for their participation in this study, and to H. Lam and M. Zhang for technical assistance. We appreciate the collaboration and discussions with R.M. Bernstein, H. Bazzi, V. Luria and K. Fantauzzo. We thank L. Langbein and J. Schweizer (Heidelberg) for generously sharing antibodies. We thank S. Ishii for discussions about P2RY5. This work was supported in part by US Public Health Service National Institutes of Health grant R01AR44924 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to A.M.C.).

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Authors and Affiliations



The study was designed and supervised by A.M.C. Laboratory work and phenotyping and pedigree ascertainment were performed by Y.S., Y.I. and M.W.; statistical analyses were performed by L.P. and D.G.; clinical observations were made by M.W., Y.S. and A.M.C.; molecular modeling of P2RY5 mutations was performed by L.S.; and Y.S., L.P. and A.M.C. contributed to the preparation of the manuscript.

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Correspondence to Angela M Christiano.

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Shimomura, Y., Wajid, M., Ishii, Y. et al. Disruption of P2RY5, an orphan G protein–coupled receptor, underlies autosomal recessive woolly hair. Nat Genet 40, 335–339 (2008).

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