Updated Genetic Testing of Primary Hyperoxaluria Type 1 in a Chinese Population:Results from a Single Center Study and a Systematic Review  

作　　者：Dun-feng DU Qian-qian LI Chen CHEN Shu-mei SHI Yuan-yuan ZHAO Ji-pin JIANG Dao-wen WANG Hui GUO Wei-jie ZHANG Zhi-shui CHEN 

机构地区：[1]Institute of Organ Transplantation,Departments of Internal Medicine and Genetic Diagnosis Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Key Laboratory of Organ Transplantation,Ministry of Health/Education,Wuhan 430030,China [3]Key Laboratory of Molecular Biophysics of the Ministry of Education,Cardio-X Center,College of Life Science and Technology and Center for Human Genome Research,Huazhong University of Science and Technology,Wuhan 430030,China [4]Institute of Hypertension,Departments of Internal Medicine and Genetic Diagnosis Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Current Medical Science》2018年第5期749-757,共9页当代医学科学（英文）

基　　金：This work was supported by the grants from the Special Project of Ministry of Health (No.201302009)and the National Natural Science Foundation of China (No. 81700300).

摘　　要：Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.

关 键 词：PRIMARY HYPEROXALURIA TYPE 1 gene SEQUENCING AGXT Chinese POPULATION 

分 类 号：R[医药卫生]