A Mosaic Hotspot PLCD1 Variant, Detectable in Blood-Derived DNA, Associated With Nevus Trichilemmocysticus

The study identifies a rare mosaic PLCD1 variant, p.(Ser745Leu), associated with nevus trichilemmocysticus, a condition characterized by multiple trichilemmal cysts. This variant was detected in both blood and cyst-derived DNA of a female proband, marking the first such detection in this condition. The research suggests a somatic origin for the variant and highlights the genetic complexity of trichilemmal cysts, which may involve a mono-allelic two-hit mechanism. Despite the absence of a common "risk allele," the findings emphasize the importance of genetic testing and sensitive sequencing technologies in understanding the etiology of trichilemmal cysts. Functional studies indicate that the variant may reduce PLCδ1 activity, potentially leading to cyst formation, and underscore the need for a multidisciplinary clinical approach due to possible systemic manifestations. Further research is necessary to explore the variant's functional impact and interactions with other genetic factors.