Abstract
Autosomal recessive hypotrichosis (LAH3) is a rare hair disorder characterized by sparse hair on scalp and the rest of the body of affected individuals. Recently mutations in a G protein-coupled receptor gene, P2RY5, located at LAH3 locus, have been reported in several families with autosomal recessive hypotrichosis simplex and woolly hair. For the present study, 22 Pakistani families with autosomal recessive hypotrichosis were enrolled. Genotyping using microsatellite markers linked to three autosomal recessive forms of hypotrichosis (LAH1, LAH2, LAH3) showed the linkage of 2 families to the LAH2 locus and 14 to the LAH3 locus. The remaining 6 families were not linked to any of the three loci. Families linked to LAH3 locus were further subjected to screening of the P2RY5 gene with direct DNA sequencing. Three previously reported variants, c.69insCATG (p.24insHfs52), c.188A > T (p.D63V) and c.565G > A (p.E189K) were observed in eight families. Four novel nonsynonymous sequence variants, c.8G > C (p.S3T), c.36insA (p.D13RfsX16), c.160insA (p.N54TfsX58) and c.436G > A (p.G146R) were found to segregate within six families.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ali G, Chishti MS, Raza SI, John P, Ahmad W (2007) A mutation in the lipase H (LIPH) gene underlie autosomal recessive hypotrichosis. Hum Genet 121:319–325
Aslam M, Chahrour MH, Razzaq A, Haque S, Yan K, Leal SM, Ahmad W (2004) A novel locus for autosomal recessive form of hypotrichosis maps to chromosome 3q26.33-q27.3. J Med Genet 41:849–852
Herzog H, Darby K, Hort YJ, Shine J (1996) Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene. Genome Res 6:858–861
Kazantseva A, Goltsov A, Zinchenko R, Grigorenko AP, Abrukova AV, Moliaka YK, Kirillov AG, Guo Z, Lyle S, Ginter EK, Rogaev EI (2006) Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH. Science 314:982–985
Kljuic A, Bazzi H, Sundberg JP, Martinez-Mir A, O’Shaughnessy R, Mahoney MG, Levy M, Montagutelli X, Ahmad W, Aita VM, Gordon D, Uitto J, Whiting D, Ott J, Fischer S, Gilliam TC, Jahoda CA, Morris RJ, Panteleyev AA, Nguyen VT, Christiano AM (2003) Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris. Cell 113:249–260
Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC (2008) G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat Genet 40:329–334
Rafiq MA, Ansar M, Mahmood S, Haque S, Faiyaz-ul-Haque M, Leal SM, Ahmad W (2004) A recurrent intragenic deletion mutation in DSG4 gene in three Pakistani families with autosomal recessive hypotrichosis. J Invest Dermatol 123:247–248
Rafique MA, Ansar M, Jamal SM, Malik S, Sohail M, Faiyaz-Ul-Haque M, Haque S, Leal SM, Ahmad W (2003) A locus for hereditary hypotrichosis localized to human chromosome 18q21.1. Eur J Hum Genet 11:623–628
Shimomura Y, Wajid M, Ishii Y, Shapiro L, Petukhova L, Gordon D, Christiano AM (2008) Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nat Genet 40:335–339
Wali A, Chishti MS, Ayub M, Yasinzai M, Kafaitullah, Ali G, John P, Ahmad W (2007) Localization of a novel autosomal recessive hypotrichosis locus (LAH3) to chromosome 13q14.11-q21.32. Clin Genet 72:23–29
Acknowledgments
We thank members of all the families for their invaluable participation and cooperation. The work presented here was funded by Higher Education Commission (HEC), Islamabad, Pakistan. Zahid Azeem, Musharraf Jelani, Gul Naz, Muhammad Tariq, Naveed Wasif, S. Kamran-ul-Hassan Naqvi were supported by indigenous PhD fellowships from HEC, Islamabad, Pakistan.
Author information
Authors and Affiliations
Corresponding author
Additional information
Z. Azeem, M. Jelani, G. Naz, M. Tariq, N. Wasif, S. Kamran-ul-Hassan Naqvi contributed equally to this work.
Rights and permissions
About this article
Cite this article
Azeem, Z., Jelani, M., Naz, G. et al. Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). Hum Genet 123, 515–519 (2008). https://doi.org/10.1007/s00439-008-0507-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-008-0507-7