Inherited defects of skull ossification often manifest as symmetric parietal foramina (PFM; MIM 168500). We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity1. Deletions of 11p11–p12 (proximal 11p deletion syndrome, P11pDS; MIM 601224; ref. 2) are characterized by multiple exostoses, attributable to haploinsufficiency of EXT2 (refs. 3,4) and PFM. Here we identify ALX4, which encodes a paired-related homeodomain transcription factor, as the PFM disease gene in P11pDS.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Wilkie, A.O.M. et al. Nature Genet. 24, 387– 390 (2000).
Bartsch, O. et al. Am. J. Hum. Genet. 58, 734– 742 (1996).
Stickens, D. et al. Nature Genet. 14, 25– 32 (1996).
Wuyts, W. et al. Hum. Mol. Genet. 5, 1547– 1557 (1996).
McGaughran, J.M., Ward, H.B. & Evans, D.G.R. J. Med. Genet. 32, 823– 824 (1995).
Wuyts, W. et al. Eur. J. Hum. Genet. 7, 579– 584 (1999).
Kutilek, S., Baxova, A., Bayer, M., Leiska, A. & Kozlowski, K. J. Paediatr. Child Health 33, 168–170 (1997).
Salamanca, A. et al. Prenat. Diagn. 14, 766– 769 (1994).
Qu, S., Li, L. & Wisdom, R. Gene 203, 217–223 ( 1997).
Hudson, R., Taniguchi-Sidle, A., Boras, K., Wiggan, O. & Hammel, P.A. Dev. Dyn. 213, 159–169 (1998).
Takahashi, M. et al. Development 125, 4417– 4425 (1998).
Qu, S. et al. Development 124, 3999–4008 (1997).
Qu, S. et al. Development 125, 2711–2721 (1998).
Wu, Y.-Q. et al. Am. J. Hum. Genet. 67, 1327– 1332 (2000).
Iseki, S., Wilkie, A.O.M. & Morriss-Kay, G.M. Development 126, 5611– 5620 (1999).
We thank the families for cooperation; R. Wisdom for the Alx4 probe; N. Elanko and S. Twigg for technical support; K. Clark for DNA sequencing; J. Peden, the OUBC group and the HGMP-RC for computing support; and P. Anslow for radiological expertise. This work was funded by the Alexander S. Onassis Foundation (Greece) and Medical Research Council (UK) (L.A.M.), The Anatomical Society of Great Britain and Ireland (I.A., G.M.M.-K.), Action Research (G.M.M.-K.) and the Wellcome Trust (A.O.M.W.).
About this article
Cite this article
Mavrogiannis, L., Antonopoulou, I., Baxová, A. et al. Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects. Nat Genet 27, 17–18 (2001) doi:10.1038/83703
Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism
Molecular Autism (2019)
MicroRNA-138 Suppresses Osteoblastic Differentiation of Valvular Interstitial Cells in Degenerative Calcific Aortic Valve Disease
International Heart Journal (2019)
Identification of a novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type-2
American Journal of Medical Genetics Part A (2018)
Developmental Dynamics (2018)