Zhou YQ, Wang XQ, Jiang J, Huang SL, Dai ZJ, Kong QQ. Novel hydroxymethylbilane synthase gene mutation identified and confirmed in a woman with acute intermittent porphyria: A case report. World J Clin Cases 2022; 10(33): 12319-12327 [PMID: 36483813 DOI: 10.12998/wjcc.v10.i33.12319]
Corresponding Author of This Article
Shu-Ling Huang, BSc, Professor, Department of Endocrinology, Dongguan Hospital of Traditional Chinese Medicine, No. 22 Songshanhu Avenue, Dongguan 523003, Guangdong Province, China. huangshuling_email@qq.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Nov 26, 2022; 10(33): 12319-12327 Published online Nov 26, 2022. doi: 10.12998/wjcc.v10.i33.12319
Novel hydroxymethylbilane synthase gene mutation identified and confirmed in a woman with acute intermittent porphyria: A case report
Yu-Qing Zhou, Xiao-Qing Wang, Jun Jiang, Shu-Ling Huang, Zhuo-Jin Dai, Qiao-Qiong Kong
Yu-Qing Zhou, Xiao-Qing Wang, Shu-Ling Huang, Department of Endocrinology, Dongguan Hospital of Traditional Chinese Medicine, Dongguan 523003, Guangdong Province, China
Jun Jiang, Department of Science and Technology ServicesChina Beijing Macro and Micro Test Biotech Co. Ltd, Beijing 100318, China
Zhuo-Jin Dai, The First Clinical Medical College, Guangdong Medical University, Zhanjiang 523003, Guangdong Province, China
Qiao-Qiong Kong, Department of Medicine, Wanjiang People's Hospital of Dongguan, Dongguan 523003, Guangdong Province, China
Author contributions: Zhou YQ, Wang XQ and Jiang J drafted and finalized the manuscript; Dai ZJ and Kong QQ revised the manuscript; Huang SL designed and supervised the study; all authors read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shu-Ling Huang, BSc, Professor, Department of Endocrinology, Dongguan Hospital of Traditional Chinese Medicine, No. 22 Songshanhu Avenue, Dongguan 523003, Guangdong Province, China. huangshuling_email@qq.com
Received: July 11, 2022 Peer-review started: July 11, 2022 First decision: September 25, 2022 Revised: October 10, 2022 Accepted: November 2, 2022 Article in press: November 2, 2022 Published online: November 26, 2022 Processing time: 134 Days and 18 Hours
Abstract
BACKGROUND
Acute intermittent porphyria (AIP) is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase(HMBS) gene. This study aimed to explore the clinical manifestations of a patient with AIP, to identify a novel HMBS gene mutation in the proband and some of her family members, and to confirm the pathogenicity of the variant.
CASE SUMMARY
A 22-year-old Chinese woman developed severe abdominal pain, lumbago, sinus tachycardia, epileptic seizure, hypertension, and weakness in lower limbs in March, 2018. Biochemical examinations indicated hypohepatia and hyponatremia. Her last menstrual period was 45 d prior to admission, and she was unaware of the pregnancy, which was confirmed by a pregnancy test after admission. Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red. Urinary porphyrin test result was positive. Based on these clinical manifestations, AIP was diagnosed. After increasing her daily glucose intake (250–300 g/d), abdominal pain was partially relieved. Three days after hospitalization, spontaneous vaginal bleeding occurred, which was confirmed as spontaneous abortion; thereafter, her clinical symptoms completely resolved. Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10 (c.648_651+1delCCAGG) in the proband and four other family members. The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay.
CONCLUSION
We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.
Core Tip: The possible pathogenic loci in a woman with acute intermittent porphyria were identified by direct sequencing, which revealed a novel heterozygous splicing mutation (c.648_651+1delCCAGG) in exon 10 of hydroxymethylbilane synthase gene. Aberrant splicing, which led to the production of a truncated protein, was confirmed through an in vitro minigene assay and bioinformatics analysis.
