Presentation Information
[OE4-1]The genetic landscape of porokeratosis in Japan
○Akiharu Kubo1,2, Sonoko Saito1, Satomi Aoki1, Kazuhiko Nakabayashi3, Hisato Suzuki4, Takashi Sasaki5, Kenichiro Hata3, Kenjiro Kosaki4, Masayuki Amagai1 (1.Department of Dermatology, Keio University School of Medicine, Tokyo, Japan, 2.Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 3.Department of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan, 4.Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan, 5.Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan)
Porokeratosis is a group of keratotic skin disorders characterized by the presence of single, few, or numerous round-shaped, variously sized skin lesions. Both sporadic and autosomal dominant cases are known. A variety of clinical phenotypes are known, including early-onset linear skin lesions (linear porokeratosis), late-onset numerous skin lesions (disseminated porokeratosis), and single or few plaque lesions of early or late-onset (Mibelli’s porokeratosis). Known causative genes (MVK, PMVK, MVD, FDPS) encode enzymes of the mevalonate pathway. In cases of germline variations of MVK, PMVK, and MVD, second-hit mutations specific to skin lesions were identified. Here, we performed a genetic analysis of 56 Japanese and 2 European patients with clinically diagnosed porokeratosis, including 5 cases of linear porokeratosis, 46 cases of disseminated porokeratosis, and 7 cases of Mibelli’s porokeratosis. Germline variants of MVD were identified in 2 cases of linear porokeratosis and 29 cases of disseminated porokeratosis, among which 22 Japanese patients had c.746T＞C (p.Phe249Ser) variant, and all 2 European patients had c.70+5G＞A variant. Germline variants of MVK or FDPS were identified in 7 and 6 cases of disseminated porokeratosis, respectively. No variants were identified in PMVK. Any germline variants of the four genes were not identified in 3 of 5 cases of linear porokeratosis, 4 of 46 cases of disseminated porokeratosis, and all 7 cases of Mibelli’s porokeratosis, suggesting that disease causative gene(s), especially for Mibelli’s porokeratosis, remain unidentified.