Journal of lower genital tract disease · 2019
Genomic Profiling of Vulvar Lichen Sclerosus Patients Shows Possible Pathogenetic Disease Mechanisms.
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Haefner Hope K, Welch Kathryn C, Rolston Aimee M, Koeppe Erika S, Stoffel Elena M, Kiel Mark J, Berger Mitchell B
Аннотация
OBJECTIVE: Vulvar lichen sclerosus (LS) is known to occur in families, suggesting a genetic link. Genomic profiling of patients with vulvar LS was investigated to find underlying pathogenetic mechanisms, with the hope that targeted therapies and future clinical research will arise.
METHODS: Two unrelated families with vulvar LS were investigated using whole-exome sequencing. Five affected sisters from 1 family were compared with their unaffected paternal aunt (unaffected control). A mother-daughter pair from a second affected family was compared with the first family. The results of the sequencing were compared with population-specific allele frequency databases to prioritize potential variants contributing to vulvar LS development.
RESULTS: Recurrent germ-line variants in 4 genes were identified as likely to be deleterious to proper protein function in all of the 7 affected patients, but not in the unaffected control. The genes with variants included CD177 (neutrophil activation), CD200 (inhibitory signal to macrophages), ANKRD18A (ankyrin repeat protein, epigenetic regulation), and LATS2 (co-repressor of androgen signaling).
CONCLUSIONS: Although many providers may see a mother and daughter with vulvar LS, this condition is rarely seen in multiple family members who are available for genetic testing. This is the first report to detail genomic profiling related to a familial association of vulvar LS.
METHODS: Two unrelated families with vulvar LS were investigated using whole-exome sequencing. Five affected sisters from 1 family were compared with their unaffected paternal aunt (unaffected control). A mother-daughter pair from a second affected family was compared with the first family. The results of the sequencing were compared with population-specific allele frequency databases to prioritize potential variants contributing to vulvar LS development.
RESULTS: Recurrent germ-line variants in 4 genes were identified as likely to be deleterious to proper protein function in all of the 7 affected patients, but not in the unaffected control. The genes with variants included CD177 (neutrophil activation), CD200 (inhibitory signal to macrophages), ANKRD18A (ankyrin repeat protein, epigenetic regulation), and LATS2 (co-repressor of androgen signaling).
CONCLUSIONS: Although many providers may see a mother and daughter with vulvar LS, this condition is rarely seen in multiple family members who are available for genetic testing. This is the first report to detail genomic profiling related to a familial association of vulvar LS.