Homozygous Inactivating Mutations in the NKX3-2 Gene Result in Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

American Journal of Human Genetics

Volumn 85, Issue 6, 2009, Pages 916-922

  Hellemans, Jan ^a   Simon, Marleen ^b   Dheedene, Annelies ^a   Alanay, Yasemin ^c   Mihci, Ercan ^d   Rifai, Laila ^e   Sefiani, Abdelaziz ^e   van Bever, Yolande ^b   Meradji, Morteza ^b   Superti Furga, Andrea ^f   Mortier, Geert ^a  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c HACETTEPE UNIVERSITY   (Turkey)

^d AKDENIZ UNIVERSITY   (Turkey)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; ARTICLE; ASPLENIA; AUTOSOMAL RECESSIVE DISORDER; AUTOSOMAL RECESSIVE INHERITANCE; BONE DYSPLASIA; CASE REPORT; CHROMOSOME 4P; FEMALE; GENE; GENE MAPPING; GENE MUTATION; GENE SEQUENCE; HAND RADIOGRAPHY; HOMOZYGOSITY; HUMAN; MALE; NKX3-2 GENE; OSSIFICATION; PERINATAL DEATH; PHYSICAL EXAMINATION; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; SPONDYLO MEGAEPIPHYSEAL METAPHYSEAL DYSPLASIA;

ADOLESCENT; ANIMALS; CHROMOSOMES, HUMAN, PAIR 4; CONSANGUINITY; DISEASE MODELS, ANIMAL; FEMALE; GENOME; HOMEODOMAIN PROTEINS; HOMOZYGOTE; HUMANS; MICE; MICROSATELLITE REPEATS; MUTATION; OSTEOCHONDRODYSPLASIAS; PEDIGREE; TRANSCRIPTION FACTORS;

ANIMALIA; MURINAE; MUS;

EID: 71149111053     PISSN: 00029297     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ajhg.2009.11.005     Document Type: Article

References (30)

1. Hirsinger E., Jouve C., Dubrulle J., and Pourquie O. Somite formation and patterning. Int. Rev. Cytol. 198 (2000) 1-65
2. Tam P.P., and Trainor P.A. Specification and segmentation of the paraxial mesoderm. Anat. Embryol. (Berl.) 189 (1994) 275-305
3. Christ B., and Ordahl C.P. Early stages of chick somite development. Anat. Embryol. (Berl.) 191 (1995) 381-396
4. Bulman M.P., Kusumi K., Frayling T.M., McKeown C., Garrett C., Lander E.S., Krumlauf R., Hattersley A.T., Ellard S., and Turnpenny P.D. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat. Genet. 24 (2000) 438-441
5. Mortier G.R., Wilkin D.J., Wilcox W.R., Rimoin D.L., Lachman R.S., Eyre D.R., and Cohn D.H. A radiographic, morphologic, biochemical and molecular analysis of a case of achondrogenesis type II resulting from substitution for a glycine residue (Gly691→Arg) in the type II collagen trimer. Hum. Mol. Genet. 4 (1995) 285-288
6. Silverman F.N., and Reiley M.A. Spondylo-megaepiphyseal-metaphyseal dysplasia: A new bone dysplasia resembling cleidocranial dysplasia. Radiology 156 (1985) 365-371
7. Agarwal P.P., Srinivasan A., Sharma R., Kabra M., and Gupta A.K. Spondylo-megaepiphyseal-metaphyseal dysplasia: An unusual bone dysplasia. Pediatr. Radiol. 33 (2003) 893-896
8. Superti-Furga A., and Unger S. Nosology and classification of genetic skeletal disorders: 2006 revision. Am. J. Med. Genet. A 143 (2007) 1-18
9. Akazawa H., Komuro I., Sugitani Y., Yazaki Y., Nagai R., and Noda T. Targeted disruption of the homeobox transcription factor Bapx1 results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation. Genes Cells 5 (2000) 499-513
10. Tribioli C., and Lufkin T. Molecular cloning, chromosomal mapping and developmental expression of BAPX1, a novel human homeobox-containing gene homologous to Drosophila bagpipe. Gene 203 (1997) 225-233
11. Collins J.S., and Schwartz C.E. Detecting polymorphisms and mutations in candidate genes. Am. J. Hum. Genet. 71 (2002) 1251-1252
12. Zeng L., Kempf H., Murtaugh L.C., Sato M.E., and Lassar A.B. Shh establishes an Nkx3.2/Sox9 autoregulatory loop that is maintained by BMP signals to induce somitic chondrogenesis. Genes Dev. 16 (2002) 1990-2005
13. Yoshiura K.I., and Murray J.C. Sequence and chromosomal assignment of human BAPX1, a bagpipe-related gene, to 4p16.1: A candidate gene for skeletal dysplasia. Genomics 45 (1997) 425-428
14. Heathcote K., Braybrook C., Abushaban L., Guy M., Khetyar M.E., Patton M.A., Carter N.D., Scambler P.J., and Syrris P. Common arterial trunk associated with a homeodomain mutation of NKX2.6. Hum. Mol. Genet. 14 (2005) 585-593
15. Goldmuntz E., Geiger E., and Benson D.W. NKX2.5 mutations in patients with tetralogy of fallot. Circulation 104 (2001) 2565-2568
16. Schott J.J., Benson D.W., Basson C.T., Pease W., Silberbach G.M., Moak J.P., Maron B.J., Seidman C.E., and Seidman J.G. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281 (1998) 108-111
17. Weir B.A., Woo M.S., Getz G., Perner S., Ding L., Beroukhim R., Lin W.M., Province M.A., Kraja A., Johnson L.A., et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 450 (2007) 893-898
18. Schorderet D.F., Nichini O., Boisset G., Polok B., Tiab L., Mayeur H., Raji B., de la Houssaye G., Abitbol M.M., and Munier F.L. Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular syndrome. Am. J. Hum. Genet. 82 (2008) 1178-1184
19. Krude H., Schutz B., Biebermann H., von Moers A., Schnabel D., Neitzel H., Tonnies H., Weise D., Lafferty A., Schwarz S., et al. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J. Clin. Invest. 109 (2002) 475-480
20. Breedveld G.J., van Dongen J.W., Danesino C., Guala A., Percy A.K., Dure L.S., Harper P., Lazarou L.P., van der Linde H., Joosse M., et al. Mutations in TITF-1 are associated with benign hereditary chorea. Hum. Mol. Genet. 11 (2002) 971-979
21. Dentice M., Cordeddu V., Rosica A., Ferrara A.M., Santarpia L., Salvatore D., Chiovato L., Perri A., Moschini L., Fazzini C., et al. Missense mutation in the transcription factor NKX2-5: A novel molecular event in the pathogenesis of thyroid dysgenesis. J. Clin. Endocrinol. Metab. 91 (2006) 1428-1433
22. Azpiazu N., and Frasch M. tinman and bagpipe: Two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev. 7 (1993) 1325-1340
23. Lettice L.A., Purdie L.A., Carlson G.J., Kilanowski F., Dorin J., and Hill R.E. The mouse bagpipe gene controls development of axial skeleton, skull, and spleen. Proc. Natl. Acad. Sci. USA 96 (1999) 9695-9700
24. Tribioli C., and Lufkin T. The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. Development 126 (1999) 5699-5711
25. Murtaugh L.C., Chyung J.H., and Lassar A.B. Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling. Genes Dev. 13 (1999) 225-237
26. Murtaugh L.C., Zeng L., Chyung J.H., and Lassar A.B. The chick transcriptional repressor Nkx3.2 acts downstream of Shh to promote BMP-dependent axial chondrogenesis. Dev. Cell 1 (2001) 411-422
27. Lengner C.J., Hassan M.Q., Serra R.W., Lepper C., van Wijnen A.J., Stein J.L., Lian J.B., and Stein G.S. Nkx3.2-mediated repression of Runx2 promotes chondrogenic differentiation. J. Biol. Chem. 280 (2005) 15872-15879
28. Rodrigo I., Hill R.E., Balling R., Munsterberg A., and Imai K. Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development 130 (2003) 473-482
29. Provot S., Kempf H., Murtaugh L.C., Chung U.I., Kim D.W., Chyung J., Kronenberg H.M., and Lassar A.B. Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. Development 133 (2006) 651-662
30. Vandesompele J., De Preter K., Pattyn F., Poppe B., Van Roy N., De Paepe A., and Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3 (2002) RESEARCH0034