摘要
AbstractHepatic phosphorylase kinase (PhK) plays an important role in glycogen metabolism by activating phosphorylase. Patients with PhK deficiency may get glycogen storage disease (GSD) type-IXa, an X-linked liver glycogenosis disease. To inform genetic counseling in a family with two affected GSD brothers, we performed a genetic analysis. The GSD in the older brother was confirmed by histological examination of a liver biopsy, which showed glycogen accumulation in liver cells. A liver biopsy was not available from the younger brother. The two patients and their parents were analyzed by whole exome sequencing. A pathogenic mutation in a gene encoding a regulatory subunit of PhK, PHKA2 located on chromosome Xp22, was identified as c.G3373A (p.E1125K) and confirmed by Sanger sequencing. The proband’s maternal grandparents and the brothers and sisters of the proband’s maternal grandfather were physically examined and genetically tested by Sanger sequencing. Pedigree analysis showed that the mother was a carrier and that the two patients inherited the mutation from their undiagnosed maternal grandfather. Moreover, among the maternal grandfather and four granduncles, three of them possessed the same mutation and four suffered from fatty liver. This is the first report of this mutation causing X-linked liver glycogenosis in a Chinese family and shows that GSD IXa is a mild form of glycogenosis in terms of clinical symptoms, indicating that GSD may be undiagnosed or underestimated. Nevertheless, to provide appropriate intervention and genetic counseling, early identification of the genetic cause is imperative. This study was approved by the Ethics Committee of First Affiliated Hospital, Hunan University of Chinese Medicine (approval No. HN-LL-ZFKY-2018-001-01) on January 12, 2018.
机构地区
Medical Laboratory Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, China,Department of Emergency Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China,First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan P
出版日期
2021年07月24日（中国期刊网平台首次上网日期，不代表论文的发表时间）
