HNF1A和葡萄糖激酶变体在青年成熟型糖尿病中的共同遗传。

IF 0.7 Q4 ENDOCRINOLOGY & METABOLISM
Daisuke Watanabe, Hideaki Yagasaki, Hiromune Narusawa, Takeshi Inukai
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引用次数: 0

摘要

摘要:青年成熟型糖尿病(MODY)是一组单基因型糖尿病,其特点是早发糖尿病伴有β细胞功能障碍的显性遗传。有关患者体内葡萄糖激酶(GCK)和肝细胞核因子 1 alpha 基因(HNF1A)变体共同遗传的报道很少。在此,我们描述了一个与 MODY 相关的单等位基因 GCK 和 HNF1A 变体组合病例。一名 10 岁的日本女孩有三代糖尿病家族史,但没有肥胖症,在一次学校筛查测试中显示尿糖水平偏高。她的糖代谢谱显示空腹血糖为 124 mg/dL,糖化血红蛋白(HbA1c)为 6.9%,C 肽免疫反应水平为 2.78 ng/mL。在 75 克口服葡萄糖耐量试验中,她的基础血糖、峰值血糖、胰岛素抵抗和β细胞功能稳态模型评估水平分别为 124 毫克/分升、210 毫克/分升(120 分钟)、1.71 和 33%。根据 GCK-MODY 的临床表型,在不使用口服降糖药的情况下,采用膳食和运动疗法来维持其空腹血糖和 HbA1c 水平。我们探讨了该病例和以往病例中 MODY 与 GCK 和 HNF1A 变体的共生遗传,发现要牢固确立表型特征,必须进行仔细的临床随访。此外,积累与 GCK 和 HNF1A 变体共生相关的经遗传学证实的 MODY 数据将有助于理解基因型与表型之间的相关性:MODY是一组单基因型糖尿病,其特点是早发糖尿病,β细胞功能障碍显性遗传。MODY2和MODY3分别由葡萄糖激酶(GCK)和肝细胞核因子1α(HNF1A)基因的杂合功能缺失变异引起,是该病最常见的形式。以前很少有报道 MODY 病例与 GCK 和 HNF1A 基因变异的共同遗传有关。要牢固确立 MODY 与 GCK 和 HNF1A 变体共生的表型特征,需要进行仔细的临床随访。积累与 GCK 和 HNF1A 变体共生相关的经基因证实的 MODY 数据将有助于了解基因型与表型之间的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Coinheritance of HNF1A and glucokinase variants in maturity-onset diabetes of the young.

Summary: Maturity-onset diabetes of the young (MODY) is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with dominant inheritance of beta-cell dysfunction. There are few reports of the coinheritance of glucokinase (GCK) and hepatocyte nuclear factor 1 alpha gene (HNF1A) variants underlying MODY in patients. Herein, we describe a case involving combinations of monoallelic GCK and HNF1A variants associated with MODY. A 10-year-old Japanese girl with a three-generation family history of diabetes without obesity showed high levels of urinary glucose during a school screening test. Her glucose metabolism profile revealed 124 mg/dL of fasting glucose, 6.9% glycated hemoglobin (HbA1c), and 2.78 ng/mL of C-peptide immunoreactivity levels. In a 75-g oral glucose tolerance test, her base glucose, peak glucose, insulin resistance, and homeostasis model assessment of beta cell function levels were 124 mg/dL, 210 mg/dL (120 min), 1.71, and 33%, respectively. Based on the clinical phenotype of GCK-MODY, alimentary and exercise therapy without oral hypoglycemic agents were used to maintain her fasting glucose and HbA1c levels. We explored the coinheritance of MODY with GCK and HNF1A variants in this and past cases and found that careful clinical follow-up is required to firmly establish phenotypic features. Moreover, the accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.

Learning points: MODY is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with the dominant inheritance of beta-cell dysfunction. MODY2 and MODY3 caused by heterozygous loss-of-function variants in the glucokinase (GCK) and hepatocyte nuclear factor 1 alpha (HNF1A) genes, respectively, are the most common forms of the disease. Few cases of MODY have previously been reported as being associated with the coinheritance of GCK and HNF1A variants. Careful clinical follow-up is required to firmly establish phenotypic features in the coinheritance of MODY with GCK and HNF1A variants. The accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.

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来源期刊
CiteScore
1.50
自引率
0.00%
发文量
142
审稿时长
9 weeks
期刊介绍: Endocrinology, Diabetes & Metabolism Case Reports publishes case reports on common and rare conditions in all areas of clinical endocrinology, diabetes and metabolism. Articles should include clear learning points which readers can use to inform medical education or clinical practice. The types of cases of interest to Endocrinology, Diabetes & Metabolism Case Reports include: -Insight into disease pathogenesis or mechanism of therapy - Novel diagnostic procedure - Novel treatment - Unique/unexpected symptoms or presentations of a disease - New disease or syndrome: presentations/diagnosis/management - Unusual effects of medical treatment - Error in diagnosis/pitfalls and caveats
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