Identification of Genetic Variants Associated With Lichen Sclerosus

Overview

Lichen Sclerosus (LS) is a common genital skin condition that severely impacts on daily living. LS occurs worldwide but may be more common in the white population. The extragenital skin is involved in about 10% of reported patients, exact numbers are not known. LS is estimated to affect 0.1-0.3% of new patients in a general hospital patient population and 1.7% of patients referred to general gynaecological practice, however, the exact prevalence and incidence is not known. LS has a major impact on the quality of life, as symptoms of itching, pain and discomfort can make it difficult to sit, walk and go to the toilet. Having sex becomes painful because of erosions and fissures (break down of the skin), sometimes impossible because of irreversible fusion (sticking together) and sclerosis (hardening) of the genital skin. There is an increased risk of genital cancer in individuals with LS, this seems higher in familial cases. Next to a genetic background leading to a dysregulation of the immune system, certain external trigger mechanisms seem to play an important role in the development of LS. In this project the investigators propose to identify pathogenic variants in novel protein-coding genes that may be involved in Lichen sclerosus using samples from families with members manifesting LS. Through elucidating underlying pathomechanims which have not yet been fully explored the development of novel treatments may be possible.

The project plan is to identify genetic variants associated with lichen sclerosus. The investigators intend to identify differences in the genome in family members affected by LS and those who are not affected by LS. The investigators hypothesize that enrollment and sequencing the genome of families with LS would lead to the discovery of novel genetic factors underlying LS. "Success" as measured by discovery of novel Mendelian genes will be inherent to our capacity to recruit a large number of families preferably with multiple affected individuals. This "opportunistic" and "somewhat untargeted" approach is essential to reach our aim of identifying novel LS-associated genes. The investigators' project does not have classical primary and secondary endpoints as one or multiple parameters are not followed and because the study is not performed within a clinical trial frame. The investigators' primary endpoint will be having sequenced the exome/genome of families with LS and solved the segregation of variants of interest in the rest of the pedigree, "Number of participants with potential LS genes". The secondary endpoint will be the identification of novel LS genes, "Number of genes associated with LS identified".