Uncovering the genetic contributions to the loose anagen hair phenotype

Hair is an essential part of one’s identity, influencing self-expression and confidence. Hair loss, as well as, other related conditions can significantly impact self-esteem and mental well-being, especially in children. One such condition, loose anagen hair syndrome, is a rare disorder where hair is poorly anchored in the follicle, making it easy to pull. Typically appearing in childhood, loose anagen hair syndrome causes hair to be sparse, dry, and difficult to manage. Though some cases improve over time, this is not always consistent and can be carried over into adulthood. Current treatment for this disorder is not very successful.

The genetic basis for loose anagen hair syndrome is complex, and the severity of the disorder is very variable among affected individuals, even in the same family. Our research sought to better understand the genetics of loose anagen hair syndrome by analyzing DNA from individuals with the condition and their families and by deeply studying the variations we see. We identified changes in seven genes that may be contributing to the disorder.

We studied a specific genetic variant in a human keratin gene (KRT32) identified in a 3-generation family affected by loose anagen hair syndrome. We suspected that this variant may be responsible for the poor anchoring of the hair shaft during its growth phase. The experimental work showed that this variant alters the anatomy of the hair cells and disrupts interactions between key hair proteins, which we expect makes hair more prone to be painlessly and effortlessly pulled out. These findings enhance our understanding of loose anagen hair syndrome and the important role played by the hair keratins in maintaining a firm anchoring of the hairs.