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 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.
Shimomura
Yutaka
Y
Department of Dermatology, Columbia University, College of Physicians & Surgeons, 630 West 168th Street, VC15 204a, New York, New York 10032, USA.
Wajid
Muhammad
M
Ishii
Yoshiyuki
Y
Shapiro
Lawrence
L
Petukhova
Lynn
L
Gordon
Derek
D
Christiano
Angela M
AM
D025063:Chromosome Disorders / Q000235:genetics; D002882:Chromosomes, Human, Pair 13; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005190:Family; D005808:Genes, Recessive; D006197:Hair / Q000473:pathology; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D010375:Pedigree; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D049368:Receptors, Lysophosphatidic Acid
D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; C082320:LPAR4 protein, human; D049368:Receptors, Lysophosphatidic Acid