MODY in Iceland is associated with mutations in HNF-1α and a novel mutation in NeuroD1
MODY in Iceland is associated with mutations in HNF-1α and a novel mutation in NeuroD1
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DOI：
10.1007/s001250100016
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发表时间：
2001-11-01
期刊：
影响因子：
8.2
通讯作者：
Arngrimsson, R
中科院分区：
文献类型：
--
作者：
Kristinsson, SY;Thorolfsdottir, ET;Arngrimsson, R
目的/假说。到目前为止，已经确定了五种不同类型的年轻人成熟型糖尿病（MODY），但突变筛查表明存在更多的MODY基因。最近，在研究II型（非胰岛素依赖型）糖尿病的遗传学中，编码胰腺细胞正常发育和功能所必需的转录因子的基因突变变得非常重要。对冰岛MODY患者及其家属进行转录因子基因突变筛查。收集了MODY患者的临床和生化资料，建立了MODY患者的家谱。连锁分析进行了染色体区域已知窝藏基因先前显示与MODY相关。通过直接测序鉴定突变。三个家庭的身份得到确认。其中两个显示出与12号染色体的连锁，并在HNF-1a基因（290fsdelC和R272C）的外显子4上携带突变。然而，第三个家族与先前描述的MODY基因没有关联，但在染色体2q32上共享了NeuroD1基因的新突变。这个突变是在密码子110上谷氨酸被赖氨酸取代。存在于蛋白质的基本结构域。在冰岛人群中已经发现了MODY受试者的突变。此外，本研究还确定了NeuroD1基因是导致第六种MODY的基因。
Aims/hypothesis. Five different types of maturity-onset diabetes of the young (MODY) have been identified until now but mutation screening suggests that more MODY genes exist. Mutations in genes encoding transcription factors essential for normal development and function of pancreatic beta cells has recently become important in studying the genetics of Type II (non-insulin-dependent) diabetes mellitus. Patients with MODY and their families in Iceland were screened for mutations in the transcription factor genes.Methods. Clinical and biochemical information on individuals with MODY was collected and their family trees constructed. Linkage analysis was carried out on chromosomal regions known to harbour genes previously shown to be associated with MODY. Mutations were identified by direct sequencing.Results. Three families were identified. Two of these showed linkage to chromosome 12 and carried mutations in exon 4 of the HNF-1a gene (290fsdelC and R272C). However, the third family showed no linkage to the previously described MODY genes but shared a novel mutation in the NeuroD1 gene on chromosome 2q32. This mutation, a glutamate to lysine substitution at codon 110. resides in the basic domain of the protein.Conclusion/interpretation. Mutations in MODY subjects have been identified in the Icelandic population. In addition this study identified the NeuroD1 gene as the gene responsible for the sixth type of MODY.