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Good Hair Day


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We worry about it falling out. We spend hundreds of dollars a year cutting and dying it, and countless hours blow-drying it. And yet scientists know little about the genetic underpinnings of hair, especially what causes it to grow too little or too much. Now, a new study in PLOS Genetics reports that a variant in one gene can cause hypertrichosis (excessive hair overgrowth), providing a welcome insight into humanity’s hair obsession.

“There are not many groups around the world that study hair biology in general and even fewer studying hair overgrowth,” said team leader Angela Christiano of Columbia University. “This study is important since, to our knowledge, it represents a first single-gene form of hypertrichosis.”

An extremely rare syndrome, hypertrichosis is characterized by lots of hair growing where it shouldn’t, such as terminal (thick, dark, dense) hairs growing on the forearm of a child, where vellum (fine, light, short) hairs should be. Previously, Christiano’s group had discovered broad genetic problems in people who had the disorder, such as copy number variants, chromosomal rearrangements, and position effects. But this time, they decided to study a single case of congenital generalized hypertrichosis terminalis (CGHT). The parents of the affected person were unaffected, indicating that the disorder was inherited in an autosomal recessive manner.

To find the gene involved, Christiano’s team performed whole exome sequencing on the patient and both parents. Bioinformatics analysis uncovered variants in 26 genes that were homozygous in the patient and heterozygous in both parents. A literature review narrowed the field to three genes, and then analysis of hair follicles narrowed the field to two. One gene, ABCA5, lies in a region implicated in five other reported cases of CGHT. Sequencing showed that the mutation found in this patient terminates the gene prematurely. Using immunofluorescence and immunohistochemistry, the team determined that ABCA5, a cholesterol transporter gene, was expressed in control human skin and hair follicles, but was greatly reduced in the patient’s hair follicles and skin.

It turns out that the ABCA5 mutation reduces lysosome function in skin cells, leading to an accumulation of cholesterol inside the endolysosome, preventing it from getting where it needs to go in the cell. The team said they don’t yet know the exact mechanism by which ABCA5 affects hair growth, but they hypothesize that interfering with cholesterol transport, which is key to many cellular functions, may be important.

“At the moment, this discovery in itself does not provide an obvious new way to treat hair diseases,” said Christiano. “However, every time a new gene is implicated in hair growth, it enhances our understanding of the hair cycle and therefore always helps to expand our thinking about ways to treat both excessive hair as well as sparse hair.”


DeStefano GM, Kurban M, Anyane-Yeboa K, Dall'Armi C, Di Paolo G, Feenstra H, Silverberg N, Rohena L, López-Cepeda LD, Jobanputra V, Fantauzzo KA, Kiuru M, Tadin-Strapps M, Sobrino A, Vitebsky A, Warburton D, Levy B, Salas-Alanis JC, Christiano AM. Mutations in the Cholesterol Transporter Gene ABCA5 Are Associated with Excessive Hair Overgrowth. PLoS Genet. 2014 May 15;10(5):e1004333.

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