The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine
文献类型：期刊论文
| 作者 | Li, Hong3,7,8; Zhao, Lihua5,6; Singh, Rani3,7,8; Ham, J. Nina4; Fadoju, Doris O.4; Bean, Lora J. H.2,3; Zhang, Yan1; Xu, Yong1; Xu, H. Eric5,6,9 ; Gambello, Michael J.3,7,8
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| 刊名 | MOLECULAR GENETICS AND METABOLISM REPORTS
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| 出版日期 | 2018-12 |
| 卷号 | 17页码:46-52 |
| 关键词 | Glucagon receptor Newborn screening GCGR mutation Hyperaminoacidemia Mahvash disease Pancreatic alpha cell hyperplasia (ACH) Pancreatic neuroendocrine tumor (PNET) |
| ISSN号 | 2214-4269 |
| DOI | 10.1016/j.ymgmr.2018.09.006 |
| 文献子类 | Article |
| 英文摘要 | Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been reported in adults with pancreatic a cell hyperplasia and PNETs. We describe a 7-year-old girl with persistent hyperaminoacidemia, notable for elevations of glutamine (normal ammonia), alanine (normal lactate), dibasic amino acids (arginine, lysine and ornithine), threonine and serine. She initially was brought to medical attention by an elevated arginine on newborn screening (NBS) and treated for presumed arginase deficiency with a low protein diet, essential amino acids formula and an ammonia scavenger drug. This treatment normalized plasma amino acids. She had intermittent emesis and anorexia, but was intellectually normal. Arginase enzyme assay and ARG1 sequencing and deletion/duplication analysis were normal. Treatments were stopped, but similar pattern of hyperaminoacidemia recurred. She also had hypercholesterolemia type IIa, with only elevated LDL cholesterol, despite an extremely lean body habitus. Exome sequencing was initially non-diagnostic. Through a literature search, we recognized the pattern of hyperaminoacidemia was strikingly similar to that reported in the Gcgr(-/-) knockout mice. Subsequently the patient was found to have an extremely elevated plasma glucagon and a novel, homozygous c.958_960del (p.Phe320del) variant in GCGR. Functional studies confirmed the pathogenicity of this variant. This case expands the clinical phenotype of GCGR defect in children and emphasizes the clinical utility of plasma amino acids in screening, diagnosis and monitoring glucagon signaling interruption. Early identification of a GCGR defect may provide an opportunity for potential beneficial treatment for an adult onset tumor predisposition disease. |
| WOS关键词 | ALPHA CELL HYPERPLASIA ; MICE ; HYPERGLUCAGONEMIA ; INHIBITION ; TUMOR ; AXIS |
| 资助项目 | Youth Innovation Promotion Association[00000000] ; Natural Science Foundation of Shanghai, China[18ZR1447800] ; National Institutes of Health, United State[DK071662] ; Fudan-SIMM Joint Research Fund, China[FU-SIMM-20174003] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Genetics & Heredity |
| 语种 | 英语 |
| WOS记录号 | WOS:000450411200014 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279483]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Li, Hong |
| 作者单位 | 1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China; 2.EGL Genet Diagnost, Tucker, GA USA; 3.Emory Univ, Dept Human Genet, Sch Med, Atlanta, GA 30322 USA; 4.Emory Univ, Sch Med, Dept Pediat, Div Pediat Endocrinol,Childrens Healthcare Atlant, Atlanta, GA 30322 USA; 5.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 6.Chinese Acad Sci, VARI SIMM Ctr Struct & Funct Drug, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 7.Childrens Healthcare Atlanta, Atlanta, GA USA; 8.Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA; 9.Van Andel Res Inst, Ctr Struct Biol & Drug Discovery, Lab Struct Sci, Grand Rapids, MI USA |
| 推荐引用方式 GB/T 7714 | Li, Hong,Zhao, Lihua,Singh, Rani,et al. The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine[J]. MOLECULAR GENETICS AND METABOLISM REPORTS,2018,17:46-52. |
| APA | Li, Hong.,Zhao, Lihua.,Singh, Rani.,Ham, J. Nina.,Fadoju, Doris O..,...&Gambello, Michael J..(2018).The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine.MOLECULAR GENETICS AND METABOLISM REPORTS,17,46-52. |
| MLA | Li, Hong,et al."The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine".MOLECULAR GENETICS AND METABOLISM REPORTS 17(2018):46-52. |
入库方式： OAI收割
来源：上海药物研究所
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