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Genomic Profiling of Vulvar Lichen Sclerosus Patients Shows Possible Pathogenetic Disease Mechanisms

Haefner, Hope K. MD1; Welch, Kathryn C. MD1,2; Rolston, Aimee M. MD, MS1; Koeppe, Erika S. MS3; Stoffel, Elena M. MD3; Kiel, Mark J. MD, PhD4; Berger, Mitchell B. MD, PhD1,5

Journal of Lower Genital Tract Disease: July 2019 - Volume 23 - Issue 3 - p 214–219
doi: 10.1097/LGT.0000000000000482
Original Research Articles: Vulva and Vagina

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.

1Department of Obstetrics and Gynecology, Michigan Medicine, Ann Arbor, MI;

2Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI;

3Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI;

4Genomenon Inc, Ann Arbor, MI; and

5Main Line Health, Philadelphia, PA

Reprint requests to: Hope K. Haefner, MD, Department of Obstetrics and Gynecology, Michigan Medicine, L4113 University Hospital South, 1500 E Medical Center Dr, Ann Arbor, MI 48109. E-mail:

The authors have reported they have no conflicts of interest.

This study was supported by an unrestricted grant from The Mosaic Foundation of Rita and Peter Heydon.

Institutional review board status was approved by the University of Michigan Institutional Review Board (HUM00043430).

Copyright © 2019 by the American Society for Colposcopy and Cervical Pathology