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

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Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes.
Human Mutation ( IF 3.3 ) Pub Date : 2020-02-17 , DOI: 10.1002/humu.23995
Elisa De Franco ₁ , Cécile Saint-Martin ₂ , Klaus Brusgaard ₃ , Amy E Knight Johnson ₄ , Lydia Aguilar-Bryan ₅ , Pamela Bowman ₁ , Jean-Baptiste Arnoux ₆ , Annette Rønholt Larsen ₇ , May Sanyoura ₈ , Siri Atma W Greeley ₈ , Raúl Calzada-León ₉ , Bradley Harman ₁ , Jayne A L Houghton ₁₀ , Elisa Nishimura-Meguro ₁₁ , Thomas W Laver ₁ , Sian Ellard _{1,

10} , Daniela Del Gaudio ₄ , Henrik Thybo Christesen _{7,

12} , Christine Bellanné-Chantelot ₂ , Sarah E Flanagan ₁

Affiliation

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Department of Genetics, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France.
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Department of Human Genetics, University of Chicago Genetic Services Laboratory, The University of Chicago, Chicago, Illinois.
Pacific Northwest Research Institute, Seattle, Washington.
Reference Center for Inherited Metabolic Diseases, Necker-Enfants Malades Hospital, Paris, France.
Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Kovler Diabetes Center, University of Chicago, Chicago, Illinois.
Pediatric Endocrinology, Endocrine Service, National Institute for Pediatrics, Mexico City, Mexico.
Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Department of Pediatric Endocrinology, Children's Hospital, National Medical Center XXI Century, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Odense Pancreas Center, Odense University Hospital, Odense, Denmark.

The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-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.

中文翻译：

先天性高胰岛素血症和糖尿病患者胰腺 β 细胞 KATP 通道基因 KCNJ11 和 ABCC8 中鉴定的变异更新。

新生儿糖尿病和高胰岛素血症最常见的遗传原因是 ABCC8 和 KCNJ11 的致病性变异。这些基因编码 β 细胞 ATP 敏感钾通道的亚基，这是葡萄糖刺激的胰岛素分泌途径的关键组成部分。这两个基因的突变导致胰岛素分泌失调；失活突变导致胰岛素分泌过多，导致先天性高胰岛素血症，而激活突变导致相反的表型糖尿病。本综述重点关注 ABCC8 和 KCNJ11 中鉴定的变异、表型谱以及对具有致病变异的个体的治疗意义。

更新日期：2020-02-17

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