PDF(Pubmed)
Abstract：
Mutations in GLIS3 cause a rare syndrome characterized by neonatal diabetes mellitus (NDM), congenital hypothyroidism, congenital glaucoma and cystic kidneys. To date, 14 mutations in GLIS3 have been reported, inherited in an autosomal recessive manner. GLIS3 is a key transcription factor involved in β-cell development, insulin expression, and development of the thyroid, eyes, liver and kidneys.
We describe non-identical twins born to consanguineous parents presenting with NDM, congenital hypothyroidism, congenital glaucoma, hepatic cholestasis, cystic kidney and delayed psychomotor development. Sequence analysis of GLIS3 identified a novel homozygous nonsense mutation, c.2392C>T, p.Gln798Ter (p.Q798*), which results in an early stop codon. The diabetes was treated with a continuous subcutaneous insulin infusion pump and continuous glucose monitoring. Fluctuating blood glucose and intermittent hypoglycemia were observed on follow-up.
This report highlights the importance of early molecular diagnosis for appropriate management of NDM. We describe a novel nonsense mutation of GLIS3 causing NDM, extend the phenotype, and discuss the challenges in clinical management. Our findings provide new areas for further investigation into the roles of GLIS3 in the pathophysiology of diabetes mellitus.
We describe non-identical twins born to consanguineous parents presenting with NDM, congenital hypothyroidism, congenital glaucoma, hepatic cholestasis, cystic kidney and delayed psychomotor development. Sequence analysis of GLIS3 identified a novel homozygous nonsense mutation, c.2392C>T, p.Gln798Ter (p.Q798*), which results in an early stop codon. The diabetes was treated with a continuous subcutaneous insulin infusion pump and continuous glucose monitoring. Fluctuating blood glucose and intermittent hypoglycemia were observed on follow-up.
This report highlights the importance of early molecular diagnosis for appropriate management of NDM. We describe a novel nonsense mutation of GLIS3 causing NDM, extend the phenotype, and discuss the challenges in clinical management. Our findings provide new areas for further investigation into the roles of GLIS3 in the pathophysiology of diabetes mellitus.
摘要：
GLIS3突变导致罕见综合征，特征为新生儿糖尿病（NDM），先天性甲状腺功能减退症,先天性青光眼和囊性肾。迄今为止,已经报道了14个GLIS3突变，以常染色体隐性方式遗传。GLIS3是参与β细胞发育的关键转录因子,胰岛素表达，和甲状腺的发育，眼睛,肝脏和肾脏。
我们描述了非同卵双胞胎出生的近亲父母出现NDM，先天性甲状腺功能减退症,先天性青光眼,肝胆汁淤积,囊性肾和精神运动发育延迟。GLIS3的序列分析鉴定了一个新的纯合无义突变，c.2392C>T，p.Gln798Ter（p.Q798*),导致早期终止密码子。糖尿病用连续皮下胰岛素输液泵和连续血糖监测治疗。随访观察到血糖波动和间歇性低血糖。
本报告强调了早期分子诊断对合理管理NDM的重要性。我们描述了引起NDM的GLIS3的新的无义突变，扩展表型，并讨论了临床管理中的挑战。我们的发现为进一步研究GLIS3在糖尿病病理生理学中的作用提供了新的领域。
我们描述了非同卵双胞胎出生的近亲父母出现NDM，先天性甲状腺功能减退症,先天性青光眼,肝胆汁淤积,囊性肾和精神运动发育延迟。GLIS3的序列分析鉴定了一个新的纯合无义突变，c.2392C>T，p.Gln798Ter（p.Q798*),导致早期终止密码子。糖尿病用连续皮下胰岛素输液泵和连续血糖监测治疗。随访观察到血糖波动和间歇性低血糖。
本报告强调了早期分子诊断对合理管理NDM的重要性。我们描述了引起NDM的GLIS3的新的无义突变，扩展表型，并讨论了临床管理中的挑战。我们的发现为进一步研究GLIS3在糖尿病病理生理学中的作用提供了新的领域。
