title: FGF5 is a crucial regulator of hair length in humans.
abstract: Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, we identified distinct pathogenic mutations within fibroblast growth factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of this gene in several additional trichomegaly families identified an additional mutation in FGF5. We further demonstrated that hair fibers from forearms of these patients were significantly longer than hairs from control individuals, with an increased proportion in the growth phase, anagen. Using hair follicle organ cultures, we show that FGF5 induces regression of the human hair follicle. We have identified FGF5 as a crucial regulator of hair growth in humans for the first time, to our knowledge, and uncovered a therapeutic target to selectively regulate eyelash growth.
authors.affiliation: Departments of Dermatology.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Higgins
authors.affiliation: Departments of Dermatology,Epidemiology.
authors.forename: Lynn
authors.initials: L
authors.lastname: Petukhova
authors.affiliation: Departments of Dermatology.
authors.forename: Sivan
authors.initials: S
authors.lastname: Harel
authors.affiliation: Departments of Dermatology.
authors.forename: Yuan Y
authors.initials: YY
authors.lastname: Ho
authors.affiliation: Departments of Dermatology.
authors.forename: Esther
authors.initials: E
authors.lastname: Drill
authors.affiliation: Biochemistry and Molecular Biophysics, and.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.affiliation: Departments of Dermatology,University of Education, Okara Campus, Lahore, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.affiliation: Departments of Dermatology,Genetics and Development, Columbia University, New York, NY 10032; and amc65@columbia.edu.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000595:Amino Acid Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006197:Hair / Q000033:anatomy & histology* / Q000254:growth & development; D018859:Hair Follicle / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D021381:Protein Transport; D017422:Sequence Analysis, DNA
chemical_list: C496449:FGF5 protein, human; D051521:Fibroblast Growth Factor 5
keywords: catagen; consanguineous families; hair cycling; next-generation sequencing