A case of neonatal type Ⅰ Alagille syndrome caused by nonsense mutation of <i>JAG</i>1 gene c.439C&gt;T

LIU Song; CHENG Rui

doi:10.16766/j.cnki.issn.1674-4152.003570

Volume 22 Issue 6

Jun. 2024

Turn off MathJax

Article Contents

Article Navigation > Chinese Journal of General Practice > 2024 > 22(6): 1077-1080

LIU Song, CHENG Rui. A case of neonatal type Ⅰ Alagille syndrome caused by nonsense mutation of JAG1 gene c.439C>T[J]. Chinese Journal of General Practice, 2024, 22(6): 1077-1080. doi: 10.16766/j.cnki.issn.1674-4152.003570

Citation:

LIU Song, CHENG Rui. A case of neonatal type Ⅰ Alagille syndrome caused by nonsense mutation of JAG1 gene c.439C>T[J]. Chinese Journal of General Practice, 2024, 22(6): 1077-1080. doi: 10.16766/j.cnki.issn.1674-4152.003570

Citation:

PDF( 2251 KB)

A case of neonatal type Ⅰ Alagille syndrome caused by nonsense mutation of JAG1 gene c.439C>T

doi: 10.16766/j.cnki.issn.1674-4152.003570

LIU Song
, CHENG Rui^,

Medical Center of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China

Funds:

82171705

Received Date: 2023-11-11
Available Online: 2024-07-22

Abstract

Abstract

To explore the clinical and genetic characteristics of a newborn suspected of Alagille syndrome. The clinical data and peripheral blood DNA of the newborn were collected. The target gene capture technology was used to detect related gene mutations, and the source of mutations was verified by Sanger sequencing. The main clinical manifestations of this newborn were cholestasis, congenital heart disease, and butterfly vertebra. Gene sequencing showed that a spontaneous heterozygous mutation named c.439C>T (p.Q147X) occurred in the JAG1 gene. This nonsense mutation leads to premature termination of the peptide chain synthesis encoding JAG1 protein. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was determined to be pathogenic (PVS1+PS2+PS4+PM2_Supporting). The newborn was diagnosed with type Ⅰ Alagille syndrome caused by a mutation in the JAG1 gene. This provides a reference basis for later diagnosis and treatment or genetic counseling.
- JAG1 gene,
- Alagille syndrome,
- Newborn

FullText(HTML)

References(18)

References

[1]	MITCHELL E, GILBERT M, LOOMES K M. Alagille syndrome[J]. Clin Liver Dis, 2018, 22(4): 625-641. doi: 10.1016/j.cld.2018.06.001
[2]	武丽娜, 孙丽莹, 朱志军, 等. Alagille综合征的临床及病理特征分析[J]. 肝脏, 2023, 28(3): 351-354, 363. https://www.cnki.com.cn/Article/CJFDTOTAL-ZUAN202303022.htm WU L N, SUN L Y, ZHU Z J, et al. Clinical and histological characteristics of patients with Alagille syndrome[J]. Chinese Hepatology, 2023, 28(3): 351-354, 363. https://www.cnki.com.cn/Article/CJFDTOTAL-ZUAN202303022.htm
[3]	SHIVARAM P S, GIRISH K P. Alagille syndrome and the liver: current insights[J]. Euroasian J Hepatogastroenterol, 2018, 8(2): 140-147.
[4]	卫慧静, 刘攀, 彭晓康, 等. 一个Alagille综合征家系的JAG1基因新变异与临床表型分析[J]. 中华医学遗传学杂志, 2021, 38(6): 545-548. doi: 10.3760/cma.j.cn511374-20200410-00249 WEI H J, LIU P, PENG X K, et al. Analysis of a novel JAG1 variant and clinical phenotype in a family affected with Alagille syndrome[J]. Chinese Journal of Medical Genetics, 2021, 38(6): 545-548. doi: 10.3760/cma.j.cn511374-20200410-00249
[5]	SEYMOUR P A, COLLIN C A, EGESKOV-MADSEN A R, et al. JAG1 modulates an oscillatory Dll1-Notch-Hes1 signaling module to coordinate growth and fate of pancreatic progenitors[J]. Dev Cell, 2020, 52(6): 731-747. doi: 10.1016/j.devcel.2020.01.015
[6]	KOHUT T J, GILBERT M A, LOOMES K M. Alagille syndrome: a focused review on clinical features, genetics, and treatment[J]. Semin Liver Dis, 2021, 41(4): 525-537. doi: 10.1055/s-0041-1730951
[7]	李红, 周俪姗, 王芳, 等. Alagille综合征临床病理及基因突变特征分析1例[J]. 华中科技大学学报(医学版), 2021, 50(2): 230-233. doi: 10.3870/j.issn.1672-0741.2021.02.017 LI H, ZHOU L S, WANG F, et al. Clinicopathological and gene mutation characteristics of Alagille syndrome: a case report[J]. Acta Med Univ Sci Technol Huazhong, 2021, 50(2): 230-233. doi: 10.3870/j.issn.1672-0741.2021.02.017
[8]	NIKNEJAD N, FOX D, BURWINKEL J L, et al. ASO silencing of a glycosyltransferase, Poglut1, improves the liver phenotypes in mouse models of Alagille syndrome[J]. Hepatology, 2023, 78(5): 1337-1351. doi: 10.1097/HEP.0000000000000380
[9]	郭丽, 赵书涛, 程映, 等. Alagille综合征患儿11例临床和遗传学分析[J]. 中华儿科杂志, 2018, 56(5): 353-358. doi: 10.3760/cma.j.issn.0578-1310.2018.05.009 GUO L, ZHAO S T, CHENG Y, et al. Clinical and genetic analysis of eleven pediatric patients with Alagille syndrome[J]. Chinese Journal of Pediatrics, 2018, 56(5): 353-358. doi: 10.3760/cma.j.issn.0578-1310.2018.05.009
[10]	陈玉霞, 詹学, 李蜀媛. Alagille综合征13例患儿特征分析[J]. 中华实用儿科临床杂志, 2020, 35(19): 1468-1471. doi: 10.3760/cma.j.cn101070-20190520-00432 CHEN Y X, ZHAN X, LI S Y. Characteristic analysis of 13 children with Alagille syndrome[J]. Chin J Appl Clin Pediatr, 2020, 35(19): 1468-1471. doi: 10.3760/cma.j.cn101070-20190520-00432
[11]	BREIKAA R M, DENMAN K, UEYAMA Y, et al. Loss of Jagged1 in mature endothelial cells causes vascular dysfunction with alterations in smooth muscle phenotypes[J]. Vascul Pharmacol, 2022, 145: 107087. DOI: 10.1016/j.vph.2022.107087.
[12]	GUO Q, HUANG F, QING Y, et al. Decreased Jagged1 expression in vascular smooth muscle cells delays endothelial regeneration in arteriovenous graft[J]. Cardiovasc Res, 2020, 116(13): 2142-2155. doi: 10.1093/cvr/cvz333
[13]	CHEN Y, LIU Y, ZHANG R, et al. Delta like non-canonical notch ligand 2 inhibits chondrogenic differentiation and cell proliferation of bone marrow mesenchymal stem cells through the notch1 signaling pathway[J]. Tissue Cell, 2023, 85: 102220. DOI: 10.1016/j.tice.2023.102220.
[14]	KRIEGERMEIER A, GREEN R. Pediatric cholestatic liver disease: review of bile acid metabolism and discussion of current and emerging therapies[J]. Front Med(Lausanne), 2020, 7: 149. DOI: 10.3389/fmed.2020.00149.
[15]	张东矗, 邓敦, 童郁, 等. 慢性乙肝患者伴骨质疏松症的危险因素研究[J]. 中华全科医学, 2020, 18(3): 432-434, 445. doi: 10.16766/j.cnki.issn.1674-4152.001265 ZHANG D C, DENG D, TONG Y, et al. The research of risk factors in chronic hepatitis B patients with osteoporosis[J]. Chinese Journal of General Practice, 2020, 18(3): 432-434, 445. doi: 10.16766/j.cnki.issn.1674-4152.001265
[16]	MUNTAHA H S T, MUNIR M, SAJID S H, et al. Ileal bile acid transporter blockers for cholestatic liver disease in pediatric patients with Alagille syndrome: a systematic review and meta-analysis[J]. J Clin Med, 2022, 11(24): 7526. DOI: 10.3390/jcm11247526.
[17]	陈琳洁, 李志军. 原发性骨质疏松症诊断与治疗[J]. 中华全科医学, 2020, 18(10): 1619-1620. http://www.zhqkyx.net/article/id/5c756c38-3de0-43c5-af82-69be383bf5b2 CHEN L J, LI Z J. Diagnosis and treatment of primary osteoporosis[J]. Chinese Journal of General Practice, 2020, 18(10): 1619-1620. http://www.zhqkyx.net/article/id/5c756c38-3de0-43c5-af82-69be383bf5b2
[18]	闵晓阳, 张亚男, 马毓梅, 等. Alagille综合征的临床特征及基因突变观察(附2例报告)[J]. 山东医药, 2020, 60(18): 17-20. doi: 10.3969/j.issn.1002-266X.2020.18.005 MIN X Y, ZHANG Y N, MA Y M, et al. Clinical features and gene mutations of Alagille syndrome (report of 2 cases)[J]. Shandong Medical Journal, 2020, 60(18): 17-20. doi: 10.3969/j.issn.1002-266X.2020.18.005

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(4)

Get Citation

PDF

XML

Article Metrics

Article views (80) PDF downloads(8)

A case of neonatal type Ⅰ Alagille syndrome caused by nonsense mutation of JAG1 gene c.439C>T

doi: 10.16766/j.cnki.issn.1674-4152.003570

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

A case of neonatal type Ⅰ Alagille syndrome caused by nonsense mutation of JAG1 gene c.439C>T

doi: 10.16766/j.cnki.issn.1674-4152.003570

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Export File

Citation

Format

Content