Microduplications upstream of MSX2 are associated with a phenocopy of cleidocranial dysplasia

Journal of Medical Genetics

Volumn 49, Issue 7, 2012, Pages 437-441

  Ott, Claus Eric ^a   Hein, Hendrikje ^b,c   Lohan, Silke ^a,b   Hoogeboom, Jeannette ^d   Foulds, Nicola ^e   Grünhagen, Johannes ^a   Stricker, Sigmar ^a,b   Villavicencio Lorini, Pablo ^a,b   Klopocki, Eva ^a,b   Mundlos, Stefan ^a,b,c  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS   (Germany)

^c Berlin Brandenburg Center for Regenerative Therapies   (Germany)

^d ERASMUS MEDICAL CENTER   (Netherlands)

^e UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR MSX2; TRANSCRIPTION FACTOR RUNX2;

ANIMAL CELL; ARTICLE; BONE AGE; CASE REPORT; CHILD; CHROMOSOME 5Q; CLEIDOCRANIAL DYSPLASIA; COMPARATIVE GENOMIC HYBRIDIZATION; COPY NUMBER VARIATION; DECIDUOUS TOOTH; ECHOCARDIOGRAPHY; GENE AMPLIFICATION; GENE CONTROL; GENE DUPLICATION; GENE OVEREXPRESSION; GENETIC ASSOCIATION; HAND RADIOGRAPHY; HEART ARRHYTHMIA; HUMAN; MALE; MINERALIZATION; NONHUMAN; PELVIS RADIOGRAPHY; POINT MUTATION; POLYMERASE CHAIN REACTION; PRESCHOOL CHILD; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SEQUENCE ANALYSIS;

ANIMALS; CELLS, CULTURED; CHICKENS; CHILD; CHILD, PRESCHOOL; CHROMOSOME DUPLICATION; CHROMOSOMES, HUMAN, PAIR 5; CLEIDOCRANIAL DYSPLASIA; CORE BINDING FACTOR ALPHA 1 SUBUNIT; DNA COPY NUMBER VARIATIONS; FEMALE; GENE EXPRESSION REGULATION; HAPLOINSUFFICIENCY; HETEROZYGOTE; HOMEODOMAIN PROTEINS; HUMANS; MALE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PHENOTYPE; POINT MUTATION; POLYMERASE CHAIN REACTION; POLYMORPHISM, SINGLE NUCLEOTIDE; SEQUENCE ANALYSIS, DNA;

EID: 84864309431     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2012-100825     Document Type: Article

References (29)

1. Mundlos S. Cleidocranial dysplasia: clinical and molecular genetics. J Med Genet 1999;36:177e82.
2. Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 1997;89:773e9.
3. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997;89:747e54.
4. Kim IS, Otto F, Zabel B, Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev 1999;80:159e70.
5. Ott CE, Leschik G, Trotier F, Brueton L, Brunner HG, Brussel W, Guillen-Navarro E, Haase C, Kohlhase J, Kotzot D, Lane A, Lee-Kirsch MA, Morlot S, Simon ME, Steichen-Gersdorf E, Tegay DH, Peters H, Mundlos S, Klopocki E. Deletions of the RUNX2 gene are present in about 10% of individuals with cleidocranial dysplasia. Hum Mutat 2010;31:E1587e93.
6. Khan A, Hyde RK, Dutra A, Mohide P, Liu P. Core binding factor beta (CBFB) haploinsufficiency due to an interstitial deletion at 16q21q22 resulting in delayed cranial ossification, cleft palate, congenital heart anomalies, and feeding difficulties but favorable outcome. Am J Med Genet A 2006;140:2349e54.
7. Kundu M, Javed A, Jeon JP, Horner A, Shum L, Eckhaus M, Muenke M, Lian JB, Yang Y, Nuckolls GH, Stein GS, Liu PP. Cbfbeta interacts with Runx2 and has a critical role in bone development. Nat Genet 2002;32:639e44.
8. Garcia-Min{ogonek}aur S, Mavrogiannis LA, Rannan-Eliya SV, Hendry MA, Liston WA, Porteous ME, Wilkie AO. Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2. Eur J Hum Genet 2003;11:892e5.
9. Mavrogiannis LA, Taylor IB, Davies SJ, Ramos FJ, Olivares JL, Wilkie AO. Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotype. Eur J Hum Genet 2006;14:151e8.
10. Wilkie AO, Tang Z, Elanko N, Walsh S, Twigg SR, Hurst JA, Wall SA, Chrzanowska KH, Maxson RE Jr. Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat Genet 2000;24:387e90.
11. Klopocki E, Lohan S, Brancati F, Koll R, Brehm A, Seemann P, Dathe K, Stricker S, Hecht J, Bosse K, Betz RC, Garaci FG, Dallapiccola B, Jain M, Muenke M, Ng VC, Chan W, Chan D, Mundlos S. Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis. Am J Hum Genet 2011;88:70e5.
12. Howard ML, Davidson EH. cis-Regulatory control circuits in development. Dev Biol 2004;271:109e18.
13. Kleinjan DA, Lettice LA. Long-range gene control and genetic disease. Adv Genet 2008;61:339e88.
14. Klopocki E, Mundlos S. Copy-number variations, noncoding sequences, and human phenotypes. Annu Rev Genomics Hum Genet 2011;12:53e72.
15. Brugger SM, Merrill AE, Torres-Vazquez J, Wu N, Ting MC, Cho JY, Dobias SL, Yi SE, Lyons K, Bell JR, Arora K, Warrior R, Maxson R. A phylogenetically conserved cisregulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development 2004;131:5153e65.
16. Cheng HC, Wang CK, Upholt WB. Transcriptional regulation of Msx2 in the AERs of developing limbs is dependent on multiple closely spaced regulatory elements. Dev Biol 2004;270:513e24.
17. Hussein SM, Duff EK, Sirard C. Smad4 and beta-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J Biol Chem 2003;278:48805e14.
18. Tan DP, Nonaka K, Nuckolls GH, Liu YH, Maxson RE, Slavkin HC, Shum L. YY1 activates Msx2 gene independent of bone morphogenetic protein signaling. Nucleic Acids Res 2002;30:1213e23.
19. Davidson D. The function and evolution of Msx genes: pointers and paradoxes. Trends Genet 1995;11:405e11.
20. Komori T. Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 2006;99:1233e9.
21. Dodig M, Tadic T, Kronenberg MS, Dacic S, Liu YH, Maxson R, Rowe DW, Lichtler AC. Ectopic Msx2 overexpression inhibits and Msx2 antisense stimulates calvarial osteoblast differentiation. Dev Biol 1999;209:298e307.
22. Liu YH, Tang Z, Kundu RK, Wu L, Luo W, Zhu D, Sangiorgi F, Snead ML, Maxson RE. Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans. Dev Biol 1999;205:260e74.
23. Shirakabe K, Terasawa K, Miyama K, Shibuya H, Nishida E. Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5. Genes Cells 2001;6:851e6.
24. Lee MH, Kim YJ, Yoon WJ, Kim JI, Kim BG, Hwang YS, Wozney JM, Chi XZ, Bae SC, Choi KY, Cho JY, Choi JY, Ryoo HM. Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter. J Biol Chem 2005;280:35579e87.
25. Satokata I, Ma L, Ohshima H, Bei M, Woo I, Nishizawa K, Maeda T, Takano Y, Uchiyama M, Heaney S, Peters H, Tang Z, Maxson R, Maas R. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet 2000;24:391e5.
26. Bernardini L, Castori M, Capalbo A, Mokini V, Mingarelli R, Simi P, Bertuccelli A, Novelli A, Dallapiccola B. Syndromic craniosynostosis due to complex chromosome 5 rearrangement and MSX2 gene triplication. Am J Med Genet A 2007;143A:2937e43.
27. Shiihara T, Kato M, Kimura T, Hayasaka K, Yamamori S, Ogata T. Craniosynostosis with extra copy of MSX2 in a patient with partial 5q-trisomy. Am J Med Genet A 2004;128A:214e16.
28. Bensoussan-Trigano V, Lallemand Y, Saint Cloment C, Robert B. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity. Dev Dyn 2011;240:1190e202.
29. Kurth I, Klopocki E, Stricker S, van Oosterwijk J, Vanek S, Altmann J, Santos HG, van Harssel JJ, de Ravel T, Wilkie AO, Gal A, Mundlos S. Duplications of noncoding elements 5' of SOX9 are associated with brachydactyly-anonychia. Nat Genet 2009;41:862e3.