Higashino Toshihide, Konomi Mayu, Kubo Akiharu, Horinosono Hiroshi, Miura Yoshinori
Graduate School of Business Administration, Keio University, Kanagawa, Japan.
Department of Dermatology, Self-Defense Forces Central Hospital, Tokyo, Japan.
J Dermatol. 2025 Mar;52(3):505-509. doi: 10.1111/1346-8138.17422. Epub 2024 Aug 12.
Acral peeling skin syndrome (APSS; MIM 609796) is a rare genodermatosis characterized by painless focal cutaneous exfoliation of the dorsal hands and feet, typically displaying autosomal recessive inheritance. While cases associated with a founder mutation in TGM5 are relatively common in European Caucasian populations, no APSS cases have been reported from Japan or other East Asian countries. In contrast, Nagashima-type palmoplantar keratosis (NPPK; MIM 615598), caused by variants in SERPINB7, is relatively common in East Asia due to founder mutations. We describe a 27-year-old Japanese woman with spontaneous focal cutaneous exfoliation of the dorsal hand following prolonged glove use, indicative of APSS. Histopathological examination revealed a cleft between the stratum corneum and stratum granulosum and within the horny layer of the epidermis, supporting this diagnosis. However, her mother and maternal uncle exhibited similar symptoms, and there was no reported consanguinity in the patient's parents or grandparents, prompting suspicion of an autosomal dominant genodermatosis. Whole-genome sequencing (WGS) revealed compound heterozygous variants in TGM5 (c.1037G>A and c.684 + 1G>A) as suspected causative variants in the patient, leading to an APSS diagnosis, the first reported in East Asia. On the other hand, her mother and maternal uncle were diagnosed with NPPK due to compound heterozygous pathogenic variants in SERPINB7 (c.796C>T and c.455-1G>A). This case highlights the complexity of diagnosing skin disorders when multiple genodermatoses with similar phenotypes exist within a pedigree. Comprehensive genetic analyses, such as whole-exome sequencing and WGS, are invaluable for identifying causative variants in such complex cases.
肢端皮肤剥脱综合征（APSS；MIM 609796）是一种罕见的遗传性皮肤病，其特征为手足背部无痛性局灶性皮肤剥脱，通常呈常染色体隐性遗传。虽然与TGM5基因的奠基者突变相关的病例在欧洲白种人群中相对常见，但日本或其他东亚国家尚未报告过APSS病例。相比之下，由SERPINB7基因变异引起的长岛型掌跖角化病（NPPK；MIM 615598）由于奠基者突变在东亚地区相对常见。我们描述了一名27岁的日本女性，在长时间戴手套后出现手背自发性局灶性皮肤剥脱，提示为APSS。组织病理学检查显示角质层与颗粒层之间以及表皮角质层内有裂隙，支持这一诊断。然而，她的母亲和舅舅也有类似症状，且患者的父母或祖父母之间没有近亲结婚的报告，这引发了对常染色体显性遗传性皮肤病的怀疑。全基因组测序（WGS）显示患者TGM5基因存在复合杂合变异（c.1037G>A和c.684+1G>A），怀疑是致病变异，从而确诊为APSS，这是东亚地区首例报告。另一方面，她的母亲和舅舅因SERPINB7基因的复合杂合致病变异（c.796C>T和c.455-1G>A）被诊断为NPPK。该病例突出了家系中存在多种表型相似的遗传性皮肤病时皮肤疾病诊断的复杂性。全面的基因分析，如全外显子测序和WGS，对于识别此类复杂病例中的致病变异非常重要。
