Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

A. Rauch, C.T. Thiel, D. Schindler, U. Wick, Y.J. Crow, A.B. Ekici, van Essen, A.J., T.O. Goecke, L. Al-Gazali, .H. Chrzanowska, C. Zweier, H.G. Brunner, K. Becker, C.J. Curry, B. Dallapiccola, K. Devriendt, A. Dörfler, E. Kinning, A. Megarbane, et al.

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).