Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome
Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome
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DOI：
10.1038/ng867
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发表时间：
2002-05-01
期刊：
影响因子：
30.8
通讯作者：
Naggert, JK
中科院分区：
文献类型：
--
作者：
Collin, GB;Marshall, JD;Naggert, JK
Alstrom综合征是一种常染色体隐性遗传病，其特征是儿童期肥胖并伴有高胰岛素血症、慢性高血糖和神经感觉缺陷（1,2）。与Alstrom综合征相关的基因可能与基因修饰因子相互作用，因为受影响个体的亚群表现出额外的特征，如扩张性心肌病(3)、肝功能障碍(4)、甲状腺功能减退(5)、男性性腺功能减退、身材矮小和轻度至中度发育迟缓，以及通常与2型糖尿病相关的继发性并发症，如高脂血症和动脉粥样硬化。我们检测到一个未表征的转录本KIAA0328，从而鉴定出ALMS1基因，该基因包含序列变异，包括4个移码突变和2个无义突变，这些突变与阿尔斯特罗姆综合征在6个不相关的家族中分离。ALMS1普遍低水平表达，与目前报道的其他基因没有显著的序列同源性。ALMS1的发现为了解Alstrom综合征及其常见疾病提供了一个切入点。
Alstrom syndrome is a homogeneous autosomal recessive disorder that is characterized by childhood obesity associated with hyperinsulinemia, chronic hyperglycemia and neurosensory deficits(1,2). The gene involved in Alstrom syndrome probably interacts with genetic modifiers, as subsets of affected individuals present with additional features such as dilated cardiomyopathy(3), hepatic dysfunction(4), hypothyroidism(5), male hypogonadism, short stature and mild to moderate developmental delay, and with secondary complications normally associated with type 2 diabetes, such as hyperlipidemia and atherosclerosis. Our detection of an uncharacterized transcript, KIAA0328, led us to identify the gene ALMS1, which contains sequence variations, including four frameshift mutations and two nonsense mutations, that segregate with Alstrom syndrome in six unrelated families. ALMS1 is ubiquitously expressed at low levels and does not share significant sequence homology with other genes reported so far. The identification of ALMS1 provides an entry point into a new pathway leading toward the understanding of both Alstrom syndrome and the common diseases that characterize it.