Rauch Anita, Thiel Christian T, Schindler Detlev, Wick Ursula, Crow Yanick J, Ekici Arif B, van Essen Anthonie J, Goecke Timm O, Al-Gazali Lihadh, Chrzanowska Krystyna H, Zweier Christiane, Brunner Han G, Becker Kristin, Curry Cynthia J, Dallapiccola Bruno, Devriendt Koenraad, Dörfler Arnd, Kinning Esther, Megarbane André, Meinecke Peter, Semple Robert K, Spranger Stephanie, Toutain Annick, Trembath Richard C, Voss Egbert, Wilson Louise, Hennekam Raoul, de Zegher Francis, Dörr Helmuth-Günther, Reis André
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Science. 2008 Feb 8;319(5864):816-9. doi: 10.1126/science.1151174. Epub 2008 Jan 3.
Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients. Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Mutations in related genes are known to cause primary microcephaly (MCPH1, CDK5RAP2, ASPM, and CENPJ).
通过研究极端身材矮小可以揭示影响人类生长的基本过程。利用基因连锁分析，我们发现21号染色体q22.3上的中心体周蛋白（PCNT）基因双等位基因功能丧失突变在25名患者中导致II型小头骨发育异常原发性侏儒症（MOPD II）。患有这种罕见遗传病的成年人平均身高为100厘米，脑容量与3个月大的婴儿相当，但智力接近正常。PCNT缺失会导致有丝分裂纺锤体紊乱和染色体错分离。已知相关基因的突变会导致原发性小头畸形（MCPH1、CDK5RAP2、ASPM和CENPJ）。
