Mihai Cristina Maria, Catrinoiu Doina, Marshall Jan, Stoicescu Ramona, Tofolean Ioan Tiberiu
Department of Pediatrics, "Ovidius" University, Faculty of Medicine, 124 Mamaia Blvd., 900527 Constanta, Romania.
J Med Life. 2008 Jul-Sep;1(3):254-61.
Over the past ten years, several studies demonstrated the connections between cilia, basal bodies and human diseases with a wide phenotypic spectrum, including randomization of body symmetry, obesity, cystic kidney diseases and retinal degeneration. Alström syndrome (OMIM 203800) first described in 1959, is a rare autosomal recessive disorder caused by mutations in a novel gene of unknown function, ALMS1, located on the short arm of chromosome 2. Central features of Alström syndrome include obesity, insulin resistance, and type 2 diabetes. About 500 individuals with Alström syndrome are known worldwide. ALMS1 is widely expressed and localizes to centrosomes and to the base of cilia. We discuss the possible molecular mechanisms, clinical features, and future therapeutic options in a patient diagnosed with this rare disease. Monogenic defects causing human obesity actually disrupt hypothalamic pathways with a profound effect on satiety and food intake. A potential contributor to obesity- cilia with impaired function or abnormal structure, creates a new link to be studied in the future, between these organelles and the genetics of obesity.
在过去十年中，多项研究表明纤毛、基体与具有广泛表型谱的人类疾病之间存在联系，这些疾病包括身体对称性紊乱、肥胖症、多囊肾病和视网膜变性。1959年首次描述的阿尔斯特伦综合征（OMIM 203800）是一种罕见的常染色体隐性疾病，由位于2号染色体短臂上的一个功能未知的新基因ALMS1发生突变引起。阿尔斯特伦综合征的主要特征包括肥胖、胰岛素抵抗和2型糖尿病。全球已知约有500名患有阿尔斯特伦综合征的患者。ALMS1广泛表达，并定位于中心体和纤毛基部。我们讨论了一名被诊断患有这种罕见疾病的患者可能的分子机制、临床特征和未来的治疗选择。导致人类肥胖的单基因缺陷实际上会破坏下丘脑通路，对饱腹感和食物摄入产生深远影响。功能受损或结构异常的纤毛是肥胖的一个潜在因素，它在这些细胞器与肥胖遗传学之间建立了一个未来有待研究的新联系。
