Mutations in the pericentrin (PCNT) gene cause primordial dwarfism.
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).
Rauch
Anita
A
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. Anita.Rauch@humgenet.uni-erlangen.de
Thiel
Christian T
CT
Schindler
Detlev
D
Wick
Ursula
U
Crow
Yanick J
YJ
Ekici
Arif B
AB
van Essen
Anthonie J
AJ
Goecke
Timm O
TO
Al-Gazali
Lihadh
L
Chrzanowska
Krystyna H
KH
Zweier
Christiane
C
Brunner
Han G
HG
Becker
Kristin
K
Curry
Cynthia J
CJ
Dallapiccola
Bruno
B
Devriendt
Koenraad
K
Dörfler
Arnd
A
Kinning
Esther
E
Megarbane
André
A
Meinecke
Peter
P
Semple
Robert K
RK
Spranger
Stephanie
S
Toutain
Annick
A
Trembath
Richard C
RC
Voss
Egbert
E
Wilson
Louise
L
Hennekam
Raoul
R
de Zegher
Francis
F
Dörr
Helmuth-Günther
HG
Reis
André
A
D000941:Antigens / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D002460:Cell Line; D018385:Centrosome / Q000502:physiology; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008126:Lod Score; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008938:Mitosis; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000502:physiology / Q000648:ultrastructure; D013577:Syndrome
D000941:Antigens; D012333:RNA, Messenger; C086178:pericentrin