Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes

被引：116

作者：

De Franco, Elisa ^{[1
]}

Saint-Martin, Cecile ^{[2
]}

Brusgaard, Klaus ^{[3
]}

Knight Johnson, Amy E. ^{[4
]}

Aguilar-Bryan, Lydia ^{[5
]}

Bowman, Pamela ^{[1
]}

Arnoux, Jean-Baptiste ^{[6
]}

Larsen, Annette Ronholt ^{[7
]}

May, Sanyoura ^{[8
]}

Greeley, Siri Atma W. ^{[8
]}

Calzada-Leon, Raul ^{[9
]}

Harman, Bradley ^{[1
]}

Houghton, Jayne A. L. ^{[10
]}

Nishimura-Meguro, Elisa ^{[11
]}

Laver, Thomas W. ^{[1
]}

Ellard, Sian ^{[1
,10
]}

del Gaudio, Daniela ^{[4
]}

Christesen, Henrik Thybo ^{[7
,12
]}

Bellanne-Chantelot, Christine ^{[2
]}

Flanagan, Sarah E. ^{[1
]}

机构：

[1] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England

[2] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Dept Genet, Paris, France

[3] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark

[4] Univ Chicago, Genet Serv Lab, Dept Human Genet, Chicago, IL 60637 USA

[5] Pacific Northwest Res Inst, 720 Broadway, Seattle, WA 98122 USA

[6] Necker Enfants Malad Hosp, Reference Ctr Inherited Metab Dis, Paris, France

[7] Odense Univ Hosp, Hans Christian Andersen Childrens Hosp, Odense, Denmark

[8] Univ Chicago, Kovler Diabet Ctr, Sect Adult & Pediat Endocrinol Diabet & Metab, Chicago, IL 60637 USA

[9] Natl Inst Pediat, Endocrine Serv, Pediat Endocrinol, Mexico City, DF, Mexico

[10] Royal Devon & Exeter NHS Fdn Trust, Dept Mol Genet, Exeter, Devon, England

[11] Inst Mexicano Seguro Social, Natl Med Ctr XXI Century, Childrens Hosp, Dept Pediat Endocrinol, Mexico City, DF, Mexico

[12] Odense Univ Hosp, Odense Pancreas Ctr, Odense, Denmark

来源：

HUMAN MUTATION | 2020年 / 41卷 / 05期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

ABCC8; congenital hyperinsulinism; K-ATP channel; KCNJ11; neonatal diabetes; SUBUNITS KIR6.2 KCNJ11; SULFONYLUREA RECEPTOR SUR1; ACTIVATING MUTATIONS; NEUROPSYCHOLOGICAL IMPAIRMENTS; FAMILIAL HYPERINSULINISM; PHENOTYPE CORRELATIONS; POTASSIUM CHANNELS; ORAL SULFONYLUREAS; E23K VARIANT; FOCAL FORMS;

D O I：

10.1002/humu.23995

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the beta-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.

引用

页码：884 / 905

页数：22

共 107 条

[41] Large-scale association studies of variants in genes encoding the pancreatic β-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes [J].