X-linked dominant protoporphyria: report of a pedigree and detection of ALAS2 gene mutations
Tao Wang, Qi Dong, Chenchen Xu, Xiping Zhou, Yuehua Liu, Hongwei Wang, Qiuning Sun, Hongzhong Jin, Heyi Zheng, Yunshu Ouyang, Chunjia Li, Rongrong Chen, Hongbing Zhang, Yaping Liu, Yongwei Wang, Guangjun Nie
Abstract
ObjectiveTo report a pedigree with X-linked dominant protoporphyria (XLDPP), and to detect 5-aminolevulinic acid synthetase 2 (ALAS2) gene mutations in this pedigree.
MethodsA 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.
ResultsA 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.
ConclusionThe deletion mutation c.1706-1709 ΔAGTG of the ALAS2 gene may be the underlying cause of XLDPP in this pedigree.
Key words:
Porphyria, erythropoietic; Genetic diseases, X-linked; DNA mutational analysis; 5-Aminolevulinic acid synthetase 2 gene; Photoaging
Contributor Information
Tao Wang
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Qi Dong
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Chenchen Xu
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Xiping Zhou
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Yuehua Liu
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Hongwei Wang
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Qiuning Sun
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Hongzhong Jin
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Heyi Zheng
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Yunshu Ouyang
Department of Ultrasound Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Chunjia Li
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
Rongrong Chen
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
Hongbing Zhang
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
Yaping Liu
Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Yongwei Wang
National Center for Nanoscience and Technology of China, Beijing 100190, China
Guangjun Nie
National Center for Nanoscience and Technology of China, Beijing 100190, China
