[1]侯思南,曾　健,顾芸芸,等.COL4A5基因c.3667G>C (p.G1223R)突变致X连锁Alport综合征家系的分子生物学实验诊断研究[J].现代检验医学杂志,2021,36(05):117-119.[doi:10.3969/j.issn.1671-7414.2021.05.026]
　HOU Si-nan,ZENG Jian,GU Yun-yun,et al.Molecular Biological Experimental Diagnostic Study of A NovelCOL4A5 Gene Mutation c.3667G>C (p.G1223R) Result in X-linkedAlport Syndrome in A Chinese Family[J].Journal of Modern Laboratory Medicine,2021,36(05):117-119.[doi:10.3969/j.issn.1671-7414.2021.05.026]
点击复制

COL4A5基因c.3667G>C (p.G1223R)突变致X连锁Alport综合征家系的分子生物学实验诊断研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第36卷
期数:
2021年05期
页码:
117-119
栏目:
研究简报·实验技术
出版日期:
2021-10-14

文章信息/Info

Title:
Molecular Biological Experimental Diagnostic Study of A NovelCOL4A5 Gene Mutation c.3667G>C (p.G1223R) Result in X-linkedAlport Syndrome in A Chinese Family
文章编号:
1671-7414（2021）05-117-03
作者:
侯思南1; 曾　健1; 顾芸芸1; 商秀娟1; 叶红玲2
（1. 南京中医药大学连云港附属医院检验科，江苏连云港 222002；2. 南京医科大学康达学院附属连云港市第二人民医院检验科，江苏连云港 222002）
Author(s):
HOU Si-nan1;  ZENG Jian1;  GU Yun-yun1;  SHANG Xiu-juan1;  YE Hong-ling2
（1. Department of Clinical Laboratory, Lianyungang Traditional Chinese Medicine Hospital, Jiangsu Lianyungang222002, China; 2. Department of Clinical Laboratory, the Second People’s Hospital of Lianyungang, JiangsuLianyungang 222002, China）
关键词:
Alport综合征; COL4A5基因; 高通量测序
分类号:
R692.39；Q754
DOI:
10.3969/j.issn.1671-7414.2021.05.026
文献标志码:
A
摘要:
目的　探讨外显子捕获高通量测序技术对X连锁Alport综合征（X-linked Alport syndrome, XLAS）的分子生物学实验诊断作用。方法　应用外显子捕获高通量测序技术对家系先证者进行基因检测，然后对检测到的变异进行生物信息学分析及家系验证，并综合分析患者临床特征和患者肾脏病理资料。结果　此家系先证者（III-1）和舅舅（II-3）携带COL4A5 c.3667G>C (p.G1223R)基因突变，先证者母亲（II-2）为此基因突变的杂合子。生物信息学分析结果显示此突变是致病的且在家系中呈共分离。结论　此研究明确了XLAS家系的致病机理并发现一新突变COL4A5 c.3667G>C (p.G1223R)，扩大了非典型AS患者COL4A5基因突变谱，对患者的诊疗选择和临床管理具有重要意义。
Abstract:
Objective　To explore molecular biological experimental diagnostic role of targeted exome-based next generationsequencing for X-linked Alport syndrome(AS). Methods　Targeted exome-based next generation sequencing were used to detectthe gene variation of the proband in the pedigree, and then the detected variations were analyzed by bioinformatics analysis andpedigree verification. The clinical characteristics and pathological data of the patients were analyzed comprehensively. Results　The proband (III-1) and uncle (II-3) in the pedigree carried COL4A5 c.3667G>C (p.G1223R) gene mutation, the mother of theproband (II-2) was a heterozygote with this mutation. Bioinformatics analysis showed that the mutation was pathogenic andcosegregate in this family. Conclusion　This study clarified the pathogenic mechanism of XLAS family and found a novelmutation COL4A5 c.3667G>C (p.G1223R). It also expanded the mutation spectrum of COL4A5 gene in atypical AS patients,which is great significance for the diagnosis and treatment selection and clinical management of patients.

参考文献/References:

[1] SAVIGE J, ARIANI F, MARI F, et al. Expert consensusguidelines for the genetic diagnosis of Alportsyndrome[J]. Pediatric Nephrology (Berlin, Germany),2019, 34(7): 1175-1189.
[2] NOZU K, NAKANISHI K, ABE Y, et al. A reviewof clinical characteristics and genetic backgroundsin Alport syndrome[J]. Clinical and ExperimentalNephrology, 2019, 23(2): 158-168.
[3] FUNK S D, LIN M H,MINER J H ,et al. Alportsyndrome and Pierson syndrome: Diseases of theglomerular basement membrane(Review)[J]. MatrixBiology, 2018, 71-72:250-261.
[4] CHEONG H I. Genetic diagnosis of Alport syndrome[J].Korean Journal of Pediatrics, 2019, 62(5): 164-165.
[5] LIU Jianhong, WEI Xiuxiu, LI Ang, et al. Novelmutations in COL4A3, COL4A4, and COL4A5 inChinese patients with Alport syndrome[J]. PLoS One,2017, 12(5): e0177685.
[6] YAMAMURA T, NOZU K, XUE Junfu, et al. Naturalhistory and genotype-phenotype correlation in femaleX-linked Alport syndrome[J]. Kidney InternationalReports, 2017, 2(5): 850-855.
[7] ZHANG Xiao, ZHANG Yanqin, ZHANG Yanmei, et al.X-linked Alport syndrome: pathogenic variant featuresand further auditory genotype-phenotype correlationsin males[J]. Orphanet Journal of Rare Diseases, 2018,13(1): 229.
[8] SHANG Shunlai, PENG Fei, WANG Tao, et al.Genotype-phenotype correlation and prognostic impactin Chinese patients with Alport syndrome[J]. MolecularGenetics & Genomic Medicine, 2019, 7(7): e00741.
[9] LI Heng, DURBIN R. Fast and accurate short readalignment with Burrows-Wheeler transform[J].Bioinformatics (Oxford, England), 2009, 25(14): 1754-1760.
[10] MCKENNA A, HANNA M, BANKS E, et al. Thegenome analysis toolkit: a MapReduce framework foranalyzing next-generation DNA sequencing data[J].Genome Research, 2010, 20(9): 1297-1303.
[11] NG P C, HENIKOFF S. Predicting deleterious aminoacid substitutions[J]. Genome Research, 2001, 11(5):863-874.
[12] ADZHUBEI I A, SCHMIDT S, PESHKIN L, et al. Amethod and server for predicting damaging missensemutations[J]. Nature Methods, 2010, 7(4): 248-249.
[13] L? Jicheng, XU Damin, PERKOVIC V, et al.Corticosteroid therapy in IgA nephropathy[J]. Journalof the American Society of Nephrology, 2012, 23(6):1108-1116.
[14] RICHARDS S, AZIZ N, BALE S, et al. Standards andguidelines for the interpretation of sequence variants:a joint consensus recommendation of the AmericanCollege of Medical Genetics and Genomics and theAssociation for Molecular Pathology[J]. Genetics inMedicine, 2015, 17(5): 405-424.
[15] FLINTER F A, CAMERON J S, CHANTLER C, et al.Genetics of classic Alport’s syndrome[J]. The Lancet,1988, 2(8618): 1005-1007.
[16] PEI Y, WATNICK T. Diagnosis and screening of autosomaldominant polycystic kidney disease[J]. Advances inChronic Kidney Disease, 2010, 17(2): 140-152.
[17] GUBLER M C. Inherited diseases of the glomerularbasement membrane[J]. Nature Clinical Practice.Nephrology, 2008, 4(1): 24-37.

相似文献/References:

[1]李 昂a,吴维青a,吕 辛a,等.高通量测序技术对常染色体隐性Alport综合征两个家系遗传特征的实验诊断研究[J].现代检验医学杂志,2018,33(03):1.[doi:10.3969/j.issn.1671-7414.2018.03.001]
　LI Anga,WU Wei-qinga,L(¨overU)Xina,et al.Experimental Diagnostic Study on the Genetic Characteristics of Two Families with Autosomal Recessive Alport Syndrome Using Next Generation Sequencing Technology[J].Journal of Modern Laboratory Medicine,2018,33(05):1.[doi:10.3969/j.issn.1671-7414.2018.03.001]

备注/Memo

备注/Memo:
基金项目：连云港市“521 高层次人才培养工程”（编号LYG52105-2018082）。
作者简介：侯思南（1982-），男，在职研究生，研究方向：临床检验诊断学，E-mail:housinan0772666@163.com。
通讯作者：叶红玲，女，主管技师，E-mail:yehongling1112@163.com。
更新日期/Last Update: 1900-01-01