Collin Gayle B, Marshall Jan D, Ikeda Akihiro, So W Venus, Russell-Eggitt Isabelle, Maffei Pietro, Beck Sebastian, Boerkoel Cornelius F, Sicolo Nicola, Martin Mitchell, Nishina Patsy M, Naggert Jürgen K
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Nat Genet. 2002 May;31(1):74-8. doi: 10.1038/ng867. Epub 2002 Apr 8.
Alström syndrome is a homogeneous autosomal recessive disorder that is characterized by childhood obesity associated with hyperinsulinemia, chronic hyperglycemia and neurosensory deficits. The gene involved in Alström syndrome probably interacts with genetic modifiers, as subsets of affected individuals present with additional features such as dilated cardiomyopathy, hepatic dysfunction, hypothyroidism, 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 Alström 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 Alström syndrome and the common diseases that characterize it.
阿尔斯特伦综合征是一种单一的常染色体隐性疾病，其特征为儿童期肥胖伴高胰岛素血症、慢性高血糖和神经感觉缺陷。与阿尔斯特伦综合征相关的基因可能与基因修饰因子相互作用，因为部分受影响个体还表现出其他特征，如扩张型心肌病、肝功能障碍、甲状腺功能减退、男性性腺功能减退、身材矮小以及轻度至中度发育迟缓，并且伴有通常与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。我们对一个未鉴定的转录本KIAA0328的检测，促使我们鉴定出基因ALMS1，该基因包含序列变异，包括四个移码突变和两个无义突变，这些变异在六个不相关的家族中与阿尔斯特伦综合征共分离。ALMS1在全身低水平表达，且与迄今报道的其他基因没有显著的序列同源性。ALMS1的鉴定为理解阿尔斯特伦综合征及其相关常见疾病的新途径提供了切入点。
