Departments of Dermatology.
Departments of Dermatology,Epidemiology.
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10648-53. doi: 10.1073/pnas.1402862111. Epub 2014 Jul 2.
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.
调控睫毛生长的机制一直不为人知。我们确定了来自巴基斯坦的两个家族，他们表现出家族性多毛症，即睫毛极度生长。我们采用外显子组测序和纯合性作图相结合的方法，在成纤维细胞生长因子 5（FGF5）中发现了导致该疾病的不同致病性突变。随后对几个额外的多毛症家族的该基因进行测序，发现了 FGF5 中的另一个突变。我们进一步证明，这些患者前臂的毛发纤维明显长于对照个体的毛发，生长期（生长期）的比例增加。通过毛囊器官培养，我们发现 FGF5 可诱导人类毛囊退化。据我们所知，这是首次发现 FGF5 是人类毛发生长的关键调节剂，并揭示了一个有选择性地调节睫毛生长的治疗靶点。
