Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

Anita Rauch; Christian T. Thiel; Detlev Schindler; Ursula Wick; Yanick J. Crow; Arif B. Ekici; Anthonie J. Van Essen; Timm O. Goecke; Lihadh Al-Gazali; Krystyna H. Chrzanowska; Christiane Zweier; Han G. Brunner; Kristin Becker; Cynthia J. Curry; Bruno Dallapiccola; Koenraad Devriendt; Arnd Dörfler; Esther Kinning; André Megarbane; Peter Meinecke; Robert K. Semple; Stephanie Spranger; Annick Toutain; Richard C. Trembath; Egbert Voss; Louise Wilson; Raoul Hennekam; Francis De Zegher; Helmuth Günther Dörr; André Reis

doi:10.1126/science.1151174

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

Anita Rauch, Christian T. Thiel, Detlev Schindler, Ursula Wick, Yanick J. Crow, Arif B. Ekici, Anthonie J. Van Essen, Timm O. Goecke, Lihadh Al-Gazali, Krystyna H. Chrzanowska, Christiane Zweier, Han G. Brunner, Kristin Becker, Cynthia J. Curry, Bruno Dallapiccola, Koenraad Devriendt, Arnd Dörfler, Esther Kinning, André Megarbane, Peter MeineckeRobert K. Semple, Stephanie Spranger, Annick Toutain, Richard C. Trembath, Egbert Voss, Louise Wilson, Raoul Hennekam, Francis De Zegher, Helmuth Günther Dörr, André Reis

Research output: Contribution to journal › Article › peer-review

Abstract

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).

Original language	English
Pages (from-to)	816-819
Number of pages	3
Journal	Science
Volume	319
Issue number	5864
DOIs	https://doi.org/10.1126/science.1151174
Publication status	Published - 8 Feb 2008

Keywords

genetics: Antigens
Apoptosis
Cell Line
physiology: Centrosome
genetics: Dwarfism
Female
cytology: Fibroblasts
Humans
Lod Score
metabolism: Lymphocytes
Male
genetics: Microcephaly
Mitosis
physiology: Mitotic Spindle Apparatus
Mutation
Pedigree
genetics: RNA, Messenger
Syndrome

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10.1126/science.1151174

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Rauch, A., Thiel, C. T., Schindler, D., Wick, U., Crow, Y. J., Ekici, A. B., Van Essen, A. J., Goecke, T. O., Al-Gazali, L., Chrzanowska, K. H., Zweier, C., Brunner, H. G., Becker, K., Curry, C. J., Dallapiccola, B., Devriendt, K., Dörfler, A., Kinning, E., Megarbane, A., ... Reis, A. (2008). Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science, 319(5864), 816-819. https://doi.org/10.1126/science.1151174

@article{b5515752ca9b45f3af5cda7f9d78cd1e,

title = "Mutations in the pericentrin (PCNT) gene cause primordial dwarfism",

abstract = "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).",

keywords = "genetics: Antigens, Apoptosis, Cell Line, physiology: Centrosome, genetics: Dwarfism, Female, cytology: Fibroblasts, Humans, Lod Score, metabolism: Lymphocytes, Male, genetics: Microcephaly, Mitosis, physiology: Mitotic Spindle Apparatus, Mutation, Pedigree, genetics: RNA, Messenger, Syndrome",

author = "Anita Rauch and Thiel, {Christian T.} and Detlev Schindler and Ursula Wick and Crow, {Yanick J.} and Ekici, {Arif B.} and {Van Essen}, {Anthonie J.} and Goecke, {Timm O.} and Lihadh Al-Gazali and Chrzanowska, {Krystyna H.} and Christiane Zweier and Brunner, {Han G.} and Kristin Becker and Curry, {Cynthia J.} and Bruno Dallapiccola and Koenraad Devriendt and Arnd D{\"o}rfler and Esther Kinning and Andr{\'e} Megarbane and Peter Meinecke and Semple, {Robert K.} and Stephanie Spranger and Annick Toutain and Trembath, {Richard C.} and Egbert Voss and Louise Wilson and Raoul Hennekam and {De Zegher}, Francis and D{\"o}rr, {Helmuth G{\"u}nther} and Andr{\'e} Reis",

year = "2008",

month = feb,

day = "8",

doi = "10.1126/science.1151174",

language = "English",

volume = "319",

pages = "816--819",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science (A A A S)",

number = "5864",

}

Rauch, A, Thiel, CT, Schindler, D, Wick, U, Crow, YJ, Ekici, AB, Van Essen, AJ, Goecke, TO, Al-Gazali, L, Chrzanowska, KH, Zweier, C, Brunner, HG, Becker, K, Curry, CJ, Dallapiccola, B, Devriendt, K, Dörfler, A, Kinning, E, Megarbane, A, Meinecke, P, Semple, RK, Spranger, S, Toutain, A, Trembath, RC, Voss, E, Wilson, L, Hennekam, R, De Zegher, F, Dörr, HG & Reis, A 2008, 'Mutations in the pericentrin (PCNT) gene cause primordial dwarfism', Science, vol. 319, no. 5864, pp. 816-819. https://doi.org/10.1126/science.1151174

TY - JOUR

T1 - Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

AU - Rauch, Anita

AU - Thiel, Christian T.

AU - Schindler, Detlev

AU - Wick, Ursula

AU - Crow, Yanick J.

AU - Ekici, Arif B.

AU - Van Essen, Anthonie J.

AU - Goecke, Timm O.

AU - Al-Gazali, Lihadh

AU - Chrzanowska, Krystyna H.

AU - Zweier, Christiane

AU - Brunner, Han G.

AU - Becker, Kristin

AU - Curry, Cynthia J.

AU - Dallapiccola, Bruno

AU - Devriendt, Koenraad

AU - Dörfler, Arnd

AU - Kinning, Esther

AU - Megarbane, André

AU - Meinecke, Peter

AU - Semple, Robert K.

AU - Spranger, Stephanie

AU - Toutain, Annick

AU - Trembath, Richard C.

AU - Voss, Egbert

AU - Wilson, Louise

AU - Hennekam, Raoul

AU - De Zegher, Francis

AU - Dörr, Helmuth Günther

AU - Reis, André

PY - 2008/2/8

Y1 - 2008/2/8

N2 - 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).

AB - 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).

KW - genetics: Antigens

KW - Apoptosis

KW - Cell Line

KW - physiology: Centrosome

KW - genetics: Dwarfism

KW - Female

KW - cytology: Fibroblasts

KW - Humans

KW - Lod Score

KW - metabolism: Lymphocytes

KW - Male

KW - genetics: Microcephaly

KW - Mitosis

KW - physiology: Mitotic Spindle Apparatus

KW - Mutation

KW - Pedigree

KW - genetics: RNA, Messenger

KW - Syndrome

U2 - 10.1126/science.1151174

DO - 10.1126/science.1151174

M3 - Article

SN - 0036-8075

VL - 319

SP - 816

EP - 819

JO - Science

JF - Science

IS - 5864

ER -

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

Abstract

Keywords

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