講演情報
[OE4-1]日本における汗孔角化症の遺伝学的ランドスケープ
○久保 亮治1,2, 齋藤 苑子1, 青木 里美1, 中林 一彦3, 鈴木 寿人4, 佐々木 貴史5, 秦 健一郎3, 小崎 健次郎4, 天谷 雅行1 (1.慶應義塾大学 医学部 皮膚科, 2.神戸大学大学院 医学研究科 内科系講座皮膚科学分野, 3.国立成育医療研究センター 周産期病態学, 4.慶應義塾大学 医学部 臨床遺伝学センター, 5.慶應義塾大学 医学部 百寿総合研究センター)
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.