Abstract
Pycnodysostosis (OMIM 265800) Is an autosomal recessive skeletal disorder first described by Maroteaux and Lamy1 that is characterized by short stature, increased bone density, delayed closure of cranial sutures, loss of the mandibular angle, dysplastic clavicles, dissolution of the terminal phalanges of the hands and feet, dental abnormalities and increased bone fragility. Patients have a typical appearance secondary to prominence of the calvarium, smallness of the facial features, prominent nose and micrognathia. The French painter, Henri de Toulouse Lautrec (1864–1901), is believed to have had the disorder2. Although more than 100 cases have been reported, we are aware of only two large consanguinous pedigrees in which the pycnodysostosis disorder segregates3–5. We have studied the segregation of the pycnodysostosis phenotype in a large consanguinous Mexican pedigree6, the clinical features of which are very similar to those described in the Arab pedigree studied by Edelson etal.3 Here, we report linkage for the pycnodysostosis phenotype in the 1cen–q21 region of human chromosome 1, and discuss candidate genes for this skeletal disorder.
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Maroteaux, P. & Lamy, M. LaPyknodysostose. Presse Med. 70, 999–1002 (1962).
Maroteaux, P. & Lamy, M. The malady of Toulouse-Lautrec. J. Am. med. Assoc. 191, 715–717 (1965).
Edelson, J.G., Obad, S., Geiger, R., On, A. & Artul, H.J Pyknodysostosis: orthopedic aspects with a description of 14 new cases. Clin. Orthop. 280, 273–276 (1992).
Sedano, H.O., Gorlin, R.J. & Anderson, V.E. Pyknodysostosis: clinical and genetic considerations. Am. J. dis. Child. 116, 70 (1968).
Sugiura, Y., Yama, Y. & Koh, J. Pyknodysostosis in Japan: report of six cases and review of Japanese literature. in Birth Defects, Original Article Series, vol. 10 (Alan R. Liss, New York, 1974).
Cossio Lozano, G.E. Thesis in Medical Genetics, Hospital Infantil de Mexico (1990).
Carmi, R. et al. Use of a DNA pooling strategy to identify a human obesity syndrome locus on chromosome 15. Hum. molec. Genet. 4, 9–13 (1995).
Gyapay, G. et al. The 1993–1994 Généthon human genetic linkage map. Nature Genet. 7, 246–339 (1994).
Yoshida, H. et al. The murine mutation osteopetrosis is in the coding region of the macrophage clony stimulating factor gene. Nature 345, 442–443 (1990).
Lathrop, G.M., Lalouel, J.-M., Julier, C. & Ott, J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).
Ladner, M.B. et al. Human CSF-1: gene structure and alternative splicing of mRNA precursors. EMBO J. 6, 2693–2698 (1987).
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Polymeropoulos, M., Ortiz De Luna, R., Ide, S. et al. The gene for pycnodysostosis maps to human chromosome 1cen–q21. Nat Genet 10, 238–239 (1995). https://doi.org/10.1038/ng0695-238
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DOI: https://doi.org/10.1038/ng0695-238
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