Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism
Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism
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DOI：
10.1038/ng1802
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发表时间：
2006-06-01
期刊：
影响因子：
30.8
通讯作者：
Julier, Cecile
中科院分区：
文献类型：
--
作者：
Senee, Valerie;Chelala, Claude;Julier, Cecile
我们最近描述了一种新的新生儿糖尿病综合征，与先天性甲状腺功能减退、先天性青光眼、肝纤维化和多囊肾相关(1)。在这里，我们证明了这种综合征是由编码GLI类似3的GLIS3突变引起的，GLI类似3是最近发现的一种转录因子(2)。在最初的家族中，我们发现了一个移码突变，预计会导致蛋白质被截断。在另外两个有不完全综合征的家庭中，我们发现受影响的个体存在影响该基因11或12 5‘-大多数外显子的缺失。胰腺和甲状腺中没有主要的转录本(两个家族都缺失)和眼睛特异的转录本(一个家族缺失)，加上一些GLIS3转录本的残留表达，似乎解释了这些人不完整的临床表现。GLIS3在早期发育阶段的胰腺中表达，在β细胞中的表达高于在其他胰腺组织中的表达。这些结果表明GLIS3在胰腺b细胞以及甲状腺、眼睛、肝脏和肾脏的发育中起着重要作用。
We recently described a new neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys(1). Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor(2). In the original family, we identified a frameshift mutation predicted to result in a truncated protein. In two other families with an incomplete syndrome, we found that affected individuals harbor deletions affecting the 11 or 12 5'-most exons of the gene. The absence of a major transcript in the pancreas and thyroid ( deletions from both families) and an eye-specific transcript ( deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals. GLIS3 is expressed in the pancreas from early developmental stages, with greater expression in beta cells than in other pancreatic tissues. These results demonstrate a major role for GLIS3 in the development of pancreatic b cells and the thyroid, eye, liver and kidney.