Bi-Allelic Mutations in LSS, Encoding Lanosterol Synthase, Cause Autosomal-Recessive Hypotrichosis Simplex

The study identified five different mutations in the LSS gene, which encodes lanosterol synthase, as the cause of autosomal-recessive hypotrichosis simplex (HS) in three unrelated families. HS is a rare hereditary alopecia with childhood onset of hair loss. The mutations were found through whole-exome sequencing in cases where the genetic cause was previously unknown. Affected individuals had very sparse scalp hair and body hair, as well as brittle eyebrows and eyelashes. The study localized the LSS protein to the hair shaft and bulb and found that while the mutant LSS proteins were mislocalized partly outside of the endoplasmic reticulum (ER), there was no difference in the overall protein level compared to the wild-type. Blood cholesterol levels in affected individuals were normal, suggesting an alternative cholesterol pathway. This discovery underscores the significance of the cholesterol biosynthetic pathway in hair follicle biology and could lead to new treatments for hair loss disorders.