How to cite this article: Kornak U, Brancati F, Le Merrer M, Lichtenbelt K, Höhne W, Tinschert S, Garaci FG, Dallapiccola B, Nürnberg P. 2010. Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss. Am J Med Genet Part A 152A:870–874.
Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss†
Article first published online: 26 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 4, pages 870–874, April 2010
How to Cite
Kornak, U., Brancati, F., Le Merrer, M., Lichtenbelt, K., Höhne, W., Tinschert, S., Garaci, F. G., Dallapiccola, B. and Nürnberg, P. (2010), Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss. Am. J. Med. Genet., 152A: 870–874. doi: 10.1002/ajmg.a.33301
- Issue published online: 26 MAR 2010
- Article first published online: 26 MAR 2010
- Manuscript Accepted: 12 DEC 2009
- Manuscript Received: 16 DEC 2008
- Deutsche Forschungsgemeinschaft (Collaborative Research Centre 577)
- Italian Ministry of Health (Ricerca Corrente 2009)
- craniometaphyseal dysplasia;
- clinical variability;
- novel mutations
Craniometaphyseal dysplasia (CMD) is a rare, sclerosing skeletal disorder caused by mutations in ANKH, which encodes a putative pyrophosphate transporting membrane protein. Six distinct ANKH mutations have been described to date. We report here on three novel mutations in simplex patients with CMD. The c.1015T>C (p.Cys339Arg) mutation found in Patient A was associated with congenital facial palsy, early-onset conductive hearing loss, and a generalized undermodeling of the long bones. The c.1172T>C (p.Leu391Pro) mutation in Patient B was associated with facial palsy, progressive conductive hearing loss, and generalized undermodeling of tubular bones. A milder phenotype without cranial nerve affection was observed in Patient C, associated with a c.1001T>G (p.Leu334Arg) mutation. All affected residues lie in evolutionarily conserved sequence blocks. These additional cases and the associated mutations contribute to an improved appreciation of the variability of this rare skeletal dysplasia. © 2010 Wiley-Liss, Inc.