Abstract:

Wang Tao, Dong Qi, Xu Chenchen, Zhou Xiping, Liu Yuehua, Wang Hongwei,Sun Qiuning, Jin Hongzhong, Zheng Heyi, Ouyang Yunshu, Li Chunjia, Chen Rongrong, Zhang Hongbing, Liu Yaping, Wang Yongwei, Nie Guangjun Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China （Wang T, Dong Q, Xu CC, Zhou XP, Liu YH, Wang HW, Sun QN, Jin HZ, Zheng HY）; Department of Ultrasound Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China （Ouyang YS）; State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China（Li CJ, Chen RR, Zhang HB）; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China （Liu YP）; National Center for Nanoscience and Technology of China, Beijing 100190, China （Wang YW, Nie GJ） Corresponding author: Liu Yuehua, Email: yuehualiu@263.net 【Abstract】 Objective To report a pedigree with X-linked dominant protoporphyria （XLDPP）, and to detect 5-aminolevulinic acid synthetase 2（ALAS2）gene mutations in this pedigree. Methods A clinical investigation was performed in a pedigree with XLDPP, and relevant data were collected from family members. A next-generation sequencing method was applied to screen possible mutation sites, and Sanger sequencing was performed to determine pathogenic gene mutations. Dermoscopy was conducted to observe skin lesions in the patients with XLDPP, and the Fotofinder system and very high frequency （VHF） ultrasound system were utilized to assess the severity of photodamage. Liver and gallbladder ultrasonography as well as blood examination were performed for all the family members. Results A deletion mutation, c.1706-1709 ΔAGTG, was detected in the ALAS2 gene on the X chromosomes of all the patients in this family, which led to replacement or loss of 19 - 20 C-terminal residues through transcriptional frameshifting, and eventually caused an increase in ALAS2 activity. In the patients with XLDPP, skin photodamage was relatively severe; protoporphyrin-induced hepatobiliary damage was observed and aggravated with age; anemia and iron deficiency occurred sometimes. Conclusion The deletion mutation c.1706-1709 ΔAGTG of the ALAS2 gene may be the underlying cause of XLDPP in this pedigree.