Mutations in the Pericentrin (PCNT) Gene Cause Primordial Dwarfism

• Published in: Science (American Association for the Advancement of Science) Vol. 319; no. 5864; pp. 816 - 819
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 08.02.2008; The American Association for the Advancement of Science
• Subjects: adults; Antigens - genetics; Antigens - metabolism; Antigens - physiology; Apoptosis; Biological and medical sciences; brain; Cell Line; Cell lines; Centrosome - physiology; Chromosomes; Diseases of the osteoarticular system; dwarfing; Dwarfism; Dwarfism - genetics; Dwarfism - pathology; Dwarfism - physiopathology; Female; Fibroblasts; Fibroblasts - cytology; Genes; Genetic disorders; Genetic mutation; Human genetics; human growth; Humans; Lod Score; loss-of-function mutation; Lymphocytes - metabolism; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Malformations of the nervous system; Medical genetics; Medical research; Medical sciences; Microcephaly; Microcephaly - genetics; Microcephaly - pathology; Microcephaly - physiopathology; Mitosis; Mitotic spindle apparatus; Mutation; Neurology; patients; Pedigree; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Spindle Apparatus - physiology; Spindle Apparatus - ultrastructure; Syndrome; Human; Nervous system diseases; Diseases of the osteoarticular system; Microcephaly; Congenital disease; Cerebral disorder; Dwarfism; Gene; Malformation; Etiology; Central nervous system disease; Genetics; Mutation; Osteochondrodysplasia
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1151174

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).