2例关节挛缩-肾功能不全-胆汁淤积综合征患儿的临床特征及遗传学分析

姜涛; 罗海燕; 欧阳文献; 唐莲; 谭艳芳; 张慧; 李双杰

doi:10.3969/j.issn.1001-5256.2022.02.029

2例关节挛缩-肾功能不全-胆汁淤积综合征患儿的临床特征及遗传学分析

DOI: 10.3969/j.issn.1001-5256.2022.02.029

a.
湖南省儿童医院肝病中心科，长沙 410007
b.
湖南省儿童医院急诊综合一科，长沙 410007

基金项目:

2019年国家医疗服务与保障能力提升(医疗卫生机构能力建设)项目

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：姜涛负责研究设计，资料分析和撰写论文；谭艳芳、唐莲、张慧参与数据收集及修改论文；罗海燕、欧阳文献、李双杰负责拟定写作思路，指导撰写论文并最后定稿。

详细信息

通信作者:
李双杰，lesjie62@vip.sina.com

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出版历程
- 收稿日期: 2021-07-07
- 录用日期: 2021-08-12
- 出版日期: 2022-02-20

Clinical features and genetic analysis of two children with arthrogryposis, renal insufficiency, and cholestasis syndrome

a.
Department of Hepatopathy Center, Hunan Children's Hospital, Changsha 410007, China
b.
Emergency Department Ⅰ, Hunan Children's Hospital, Changsha 410007, China

Research funding:

2019 National Medical Service and Guarantee Capacity Improvement (Capacity Building of Medical and Health Institutions) Project

More Information

Corresponding author: LI Shuangjie, lesjie62@vip.sina.com

摘要

- 胆汁淤积, 肝内 /
- 关节挛缩 /
- 肾功能不全 /
- 体征和症状 /
- 基因检测
- Cholestasis, Intrahepatic /
- Arthrogryposis /
- Renal Insufficiency /
- Signs and Symptoms /
- Genetic Testing

HTML全文

图 1 2例ARC综合征患儿基因图谱

注：a，病例1患儿为VPS33B基因c.1567C＞T和c.1726T＞C复合杂合突变；b，病例2患儿为VPS33B基因c.1030+1G＞A和c.1099G＞A复合杂合突变。

下载: 全尺寸图片幻灯片

表 1 2例ARC综合征患儿入院后初次肝功能指标检查结果

患儿	TBil (μmol/L)	DBil (μmol/L)	总蛋白(g/L)	白蛋白(g/L)	ALT (U/L)	AST (U/L)	总胆汁酸(μmol/L)	GGT (U/L)
病例1	163.7	129.4	55.8	32.6	70.3	86.7	97.3	25.0
病例2	225.8	147.7	46.7	32.3	135.2	134.8	68.3	23.5
正常值	3.4~17	0~6	55~80	35~55	0~40	0~40	0~9.67	0~50

下载: 导出CSV

表 2 2例ARC综合征患儿基因检测结果

患儿	染色体位置	核苷酸改变	氨基酸改变	状态	来源	文献报道	变异类型
病例1	chr15∶91543734	c.1567C＞T	p.R523^*	杂合	母亲	有	无义突变
病例1	chr15∶91542955	c.1726T＞C	p.C576R	杂合	新发	有	错义突变
病例2	chr15∶91548923	c.1030+1G＞A	-	杂合	母亲	无	剪切位点
病例2	chr15∶91548616	c.1099G＞A	p.E367K	杂合	父亲	无	错义突变

下载: 导出CSV

参考文献(19)

[1]	FAWAZ R, BAUMANN U, EKONG U, et al. Guideline for the evaluation of cholestatic jaundice in infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition[J]. J Pediatr Gastroenterol Nutr, 2017, 64(1): 154-168. DOI: 10.1097/MPG.0000000000001334.
[2]	LI AQ, DONG Y, XU ZQ, et al. Progressive familial intrahepatic cholestasis type 3: A report of two cases in one pedigree[J]. J Clin Hepatol, 2020, 36(7): 1601-1604. DOI: 10.3969/j.issn.1001-5256.2020.07.032. 李爱芹, 董漪, 徐志强, 等. 进行性家族性肝内胆汁淤积症3型一家系2例报告[J]. 临床肝胆病杂志, 2020, 36(7): 1601-1604. DOI: 10.3969/j.issn.1001-5256.2020.07.032.
[3]	QIU YL, LIU T, ABUDUXIKUER K, et al. Novel missense mutation in VPS33B is associated with isolated low gamma-glutamyltransferase cholestasis: Attenuated, incomplete phenotype of arthrogryposis, renal dysfunction, and cholestasis syndrome[J]. Hum Mutat, 2019, 40(12): 2247-2257. DOI: 10.1002/humu.23770.
[4]	BRETSCHER-DUTOIT C. Familial bile duct malformations associated with tubular renal insufficiency: A.R. Lutz-Richner and R. F. Landolt. Helv. Paediatr. Acta 28: 1-12 (March), 1973[J]. J Pediatr Surg, 1974, 9(4): 577. DOI: 10.1016/S0022-3468(74)80079-5.
[5]	HUANG DG, LIU JJ, GUO L, et al. Clinical features and VPS33B mutations in a family affected by arthrogryposis, renal dysfunction, and cholestasis syndrome[J]. Chin J Contemp Pediatr, 2017, 19(10): 1077-1082. DOI: 10.7499/j.issn.1008-8830.2017.10.009. 黄大桂, 刘佳佳, 郭丽, 等. 关节挛缩、肾功能不全和胆汁淤积综合征一家系临床特点及VPS33B基因突变分析[J]. 中国当代儿科杂志, 2017, 19(10): 1077-1082. DOI: 10.7499/j.issn.1008-8830.2017.10.009.
[6]	RICHARDS S, AZIZ N, BALE S, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. DOI: 10.1038/gim.2015.30.
[7]	RIGGS ER, ANDERSEN EF, CHERRY AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)[J]. Genet Med, 2020, 22(2): 245-257. DOI: 10.1038/s41436-019-0686-8.
[8]	SMITH H, GALMES R, GOGOLINA E, et al. Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome[J]. Hum Mutat, 2012, 33(12): 1656-1664. DOI: 10.1002/humu.22155.
[9]	FU K, WANG C, GAO Y, et al. Metabolomics and lipidomics reveal the effect of hepatic Vps33b deficiency on bile acids and lipids metabolism[J]. Front Pharmacol, 2019, 10: 276. DOI: 10.3389/fphar.2019.00276.
[10]	GISSEN P, JOHNSON CA, MORGAN NV, et al. Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome[J]. Nat Genet, 2004, 36(4): 400-404. DOI: 10.1038/ng1325.
[11]	WANG JS, ZHAO J, LI LT. ARC syndrome with high GGT cholestasis caused by VPS33B mutations[J]. World J Gastroenterol, 2014, 20(16): 4830-4834. DOI: 10.3748/wjg.v20.i16.4830.
[12]	DUONG MD, ROSE CM, REIDY KJ, et al. An uncommon case of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome and review of the renal involvement: Answers[J]. Pediatr Nephrol, 2020, 35(2): 249-251. DOI: 10.1007/s00467-019-04338-z.
[13]	LEE MJ, SUH CR, SHIN JH, et al. A novel VPS33B variant identified by exome sequencing in a patient with arthrogryposis-renal dysfunction-cholestasis syndrome[J]. Pediatr Gastroenterol Hepatol Nutr, 2019, 22(6): 581-587. DOI: 10.5223/pghn.2019.22.6.581.
[14]	GISSEN P, TEE L, JOHNSON CA, et al. Clinical and molecular genetic features of ARC syndrome[J]. Hum Genet, 2006, 120(3): 396-409. DOI: 10.1007/s00439-006-0232-z.
[15]	AGAKIDOU E, AGAKIDIS C, KAMBOURIS M, et al. A novel mutation of VPS33B gene associated with incomplete arthrogryposis-renal dysfunction-cholestasis phenotype[J]. Case Rep Genet, 2020, 2020: 8872294. DOI: 10.1155/2020/8872294.
[16]	ROSALES A, MHIBIK M, GISSEN P, et al. Severe renal Fanconi and management strategies in arthrogryposis-renal dysfunction-cholestasis syndrome: A case report[J]. BMC Nephrol, 2018, 19(1): 144. DOI: 10.1186/s12882-018-0926-1.
[17]	FOKKEMA IF, TASCHNER PE, SCHAAFSMA GC, et al. LOVD v. 2.0: The next generation in gene variant databases[J]. Hum Mutat, 2011, 32(5): 557-563. DOI: 10.1002/humu.21438.
[18]	LI LT, ZHAO J, CHEN R, et al. Two novel VPS33B mutations in a patient with arthrogryposis, renal dysfunction and cholestasis syndrome in mainland China[J]. World J Gastroenterol, 2014, 20(1): 326-329. DOI: 10.3748/wjg.v20.i1.326.
[19]	DEL BRÍO CASTILLO R, SQUIRES JE, MCKIERNAN PJ. A novel mutation in VPS33B gene causing a milder ARC syndrome phenotype with prolonged survival[J]. JIMD Rep, 2019, 47(1): 4-8. DOI: 10.1002/jmd2.12027.