Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

被引：314

作者：

Rauch, Anita ^{[1
]}

Thiel, Christian T. ^{[1
]}

Schindler, Detlev ^{[2
]}

Wick, Ursula ^{[1
]}

Crow, Yanick J. ^{[3
]}

Ekici, Arif B. ^{[1
]}

van Essen, Anthonie J. ^{[4
]}

Goecke, Timm O. ^{[5
]}

Al-Gazali, Lihadh ^{[6
]}

Chrzanowska, Krystyna H. ^{[7
]}

Zweier, Christiane ^{[1
]}

Brunner, Han G. ^{[8
]}

Becker, Kristin ^{[9
,10
]}

Curry, Cynthia J. ^{[11
,12
]}

Dallapiccola, Bruno ^{[13
,14
]}

Devriendt, Koenraad ^{[15
]}

Doerfler, Arnd ^{[16
]}

Kinning, Esther ^{[17
]}

Megarbane, Andre ^{[18
]}

Meinecke, Peter ^{[19
]}

Semple, Robert K. ^{[20
]}

Spranger, Stephanie ^{[21
]}

Toutain, Annick ^{[22
]}

Trembath, Richard C. ^{[23
]}

Voss, Egbert ^{[24
]}

Wilson, Louise ^{[25
]}

Hennekam, Raoul ^{[25
,26
,27
]}

de Zegher, Francis ^{[28
]}

Doerr, Helmuth-Guenther ^{[29
]}

Reis, Andre ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-8520 Erlangen, Germany

[2] Univ Wurzburg, Dept Human Genet, D-8700 Wurzburg, Germany

[3] St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England

[4] Univ Groningen, Dept Genet, Univ Med Ctr Groningen, Groningen, Netherlands

[5] Univ Dusseldorf, Inst Humangenet & Anthropol, Dusseldorf, Germany

[6] United Arab Emirates Univ, Fac Med, Al Ain, U Arab Emirates

[7] Childrens Mem Hlth Inst, Dept Med Genet, Warsaw, Poland

[8] Radboud Univ Nijmegen, Dept Human Genet, Nijmegen Ctr Mol Life Sci, Nijmegen Med Ctr, Nijmegen, Netherlands

[9] Glan Clwyd Gen Hosp, N Wales Clin Genet Serv, Rhyl, Wales

[10] Univ Wales Hosp, Inst Med Genet, Cardiff, Wales

[11] Genet Med Cent Calif, Fresno, CA USA

[12] Univ Calif San Francisco, San Francisco, CA 94143 USA

[13] San Giovanni Rotondo & CSS Mendel Inst, IRCCS, Rome, Italy

[14] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy

[15] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium

[16] Univ Erlangen Nurnberg, Dept Neuroradiol, Univ Hosp Erlangen, Erlangen, Germany

[17] Leicester Royal Infirm, Dept Clin Genet, Leicester, Leics, England

[18] Univ St Joseph, Unite Genet Med, Fac Med, Beirut, Lebanon

[19] Altonaer Kinderkrankenhaus, Abt Med Genet, Hamburg, Germany

[20] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2QQ, England

[21] Praxis Humangenet, Bremen, Germany

[22] Bretonneau Univ Hosp, Dept Genet, Tours, France

[23] Kings Coll London, Dept Med & Mol Genet, Sch Med, London WC2R 2LS, England

[24] Cnopfs Pediat Hosp, Nurnberg, Germany

[25] Great Ormond St Hosp Sick Children, Dept Clin Genet, London WC1N 3JH, England

[26] UCL, Inst Child Hlth, Clin & Mol Genet Unit, London, England

[27] Univ Amsterdam, Dept Paediat, Amsterdam, Netherlands

[28] Katholieke Univ Leuven, Dept Woman & Child, Louvain, Belgium

[29] Univ Erlangen Nurnberg, Dept Pediat & Adolescent Med, Erlangen, Germany

来源：

SCIENCE | 2008年 / 319卷 / 5864期

基金：

英国惠康基金;

关键词：

II MOPD-II; CALMODULIN-BINDING PROTEIN; HOMO-FLORESIENSIS; CLINICAL REPORT; BRAIN; ANEUPLOIDY; HOMININ; STROKE; LB1;

D O I：

10.1126/science.1151174

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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).

引用

页码：816 / 819

页数：4

共 27 条

[1] Homo floresiensis:: Microcephalic, pygmoid, Australopithecus, or Homo? [J].

Argue, Debbie ;

Donlon, Denise ;

Groves, Colin ;

Wright, Richard .

JOURNAL OF HUMAN EVOLUTION, 2006, 51 (04) :360-374

[2] Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: Clinical report and review of cerebral vascular anomalies [J].

Brancati, F ;

Castori, M ;

Mingarelli, R ;

Dallapiccola, B .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2005, 139A (03) :212-215

[3] A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia [J].

Brown, P ;

Sutikna, T ;

Morwood, MJ ;

Soejono, RP ;

Jatmiko ;

Saptomo, EW ;

Due, RA .

NATURE, 2004, 431 (7012) :1055-1061

[4] The fellowship of the hobbit [J].

Culotta, Elizabeth .

SCIENCE, 2007, 317 (5839) :740-742

[5] Chromosome segregation and aneuploidy series: Centrosome control of the cell [J].

Doxsey, S ;

Zimmerman, W ;

Mikule, K .

TRENDS IN CELL BIOLOGY, 2005, 15 (06) :303-311

[6] Response to Comment on "The brain of LB1, Homo floresiensis" [J].

Falk, D ;

Hildebolt, C ;

Smith, K ;

Morwood, MJ ;

Sutikna, T ;

Jatmiko ;

Saptomo, EW ;

Brunsden, B ;

Prior, F .

SCIENCE, 2006, 312 (5776)

[7] Response to comment on "The brain of LB1, Homo floresiensis" [J].

Falk, D ;

Hildebolt, C ;

Smith, K ;

Morwood, MJ ;

Sutikna, T ;

Jatmiko ;

Saptomo, EW ;

Brunsden, B ;

Prior, F .

SCIENCE, 2005, 310 (5746)

[8] The brain of LB1, Homo floresiensis [J].

Falk, D ;

Hildebolt, C ;

Smith, K ;

Morwood, MJ ;

Sutikna, T ;

Brown, P ;

Jatmiko ;

Saptomo, EW ;

Brunsden, B ;

Prior, F .

SCIENCE, 2005, 308 (5719) :242-245

[9] Brain shape in human microcephalics and Homo floresiensis [J].

Falk, Dean ;

Hildebolt, Charles ;

Smith, Kirk ;

Morwood, M. J. ;

Sutikna, Thomas ;

Jatmiko ;

Saptomo, E. Wayhu ;

Imhof, Herwig ;

Seidler, Horst ;

Prior, Fred .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (07) :2513-2518

[10] Identification of a human centrosomal calmodulin-binding protein that shares homology with pericentrin [J].

Flory, MR ;

Moser, MJ ;

Monnat, RJ ;

Davis, TN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (11) :5919-5923

← 1 2 3 →