近期的《美国人类遗传学杂志》（American Journal of Human Genetics）刊登了英国伦敦大学一项最新研究，研究人员通过基因工程对于携带有人类21号染色体的老鼠胚胎干细胞进行了研究，结果发现，额外的21号染色体会干扰一个名为NRSF 或 REST的关键性的调控基因。同时，研究人员还识别出了人类21号染色体上的一个基因DYRK1A，该基因数量的增加会引发唐氏综合症的症状。
唐氏综合症是人类最常见、也是第一种被确认的染色体病。主要特征为低智商，并伴有特殊面容。长期以来，人们一直认为大部分唐氏综合症患者是由于在配子（生殖细胞）形成期或合子期（约在受精后24小时内）细胞内多了一条21号染色体所致。但是，关于这种疾病造成脑发育异常的精细遗传机制，一直不为人所了解。
在最新的研究中，科学家对经过基因工程改良而携带有人类21号染色体的老鼠胚胎干细胞进行了研究。结果发现，额外的21号染色体会干扰一个名为NRSF 或 REST的关键性调控基因，然后该受影响的基因会再去影响其它许多在胚胎干细胞阶段控制细胞正常发育的基因。此外，他们还识别出了人类21号染色体上的一个基因DYRK1A，研究发现该基因数量增加会引起唐氏综合症的症状。
研究人员下一步将对在胚胎干细胞阶段控制细胞正常发育的基因研究，希望能为唐氏综合症疾病的基因治疗开辟新的路径。（生物谷Bioon.com）
生物谷推荐原始出处：
American Journal of Human Genetics，doi:10.1016/j.ajhg.2008.03.001，Rikke S. M?ller, Zeynep Tümer, and Vera M. Kalscheuer
Truncation of the Down Syndrome Candidate Gene DYRK1A in Two Unrelated Patients with Microcephaly
Rikke S. M?ller1, 2, Sabine Kübart3, Maria Hoeltzenbein3, Babett Heye4, Ida Vogel5, Christian P. Hansen2, Corinna Menzel3, Reinhard Ullmann3, Niels Tommerup1, Hans-Hilger Ropers3, Zeynep Tümer1, , and Vera M. Kalscheuer3
1Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark 2Danish Epilepsy Centre, Dianalund, Kolonivej 1, 4293 Dianalund, Denmark 3Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany 4Institut für Soziale P?diatrie und Jugendmedizin der Universit?t München, Abteilung Genetik, Kinderzentrum München, 81377 München, Germany 5Department of Clinical Genetics, Aarhus University Hospital, The Bartholin Building, DK-8000 Aarhus C, Denmark
We have identified and characterized two unrelated patients with prenatal onset of microcephaly, intrauterine growth retardation, feeding problems, developmental delay, and febrile seizures/epilepsy who both carry a de novo balanced translocation that truncates the DYRK1A gene at chromosome 21q22.2. DYRK1A belongs to the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family, which is highly conserved throughout evolution. Given its localization in both the Down syndrome critical region and in the minimal region for partial monosomy 21, the gene has been studied intensively in animals and in humans, and DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with these syndromes. In the present study, we show that truncating mutations of DYRK1A result in a clinical phenotype including microcephaly.
