How to cite this article: Zajac A, Baek S-H, Salhab I, Radecki MA, Kim S, Hakonarson H, Nah H-D. 2010. Novel ANKH mutation in a patient with sporadic craniometaphyseal dysplasia. Am J Med Genet Part A 152A:770–776.
Novel ANKH mutation in a patient with sporadic craniometaphyseal dysplasia†
Version of Record online: 22 FEB 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 3, pages 770–776, March 2010
How to Cite
Zajac, A., Baek, S.-H., Salhab, I., Radecki, M. A., Kim, S., Hakonarson, H. and Nah, H.-D. (2010), Novel ANKH mutation in a patient with sporadic craniometaphyseal dysplasia. Am. J. Med. Genet., 152A: 770–776. doi: 10.1002/ajmg.a.33317
- Issue online: 22 FEB 2010
- Version of Record online: 22 FEB 2010
- Manuscript Accepted: 18 DEC 2009
- Manuscript Received: 28 APR 2009
- NIH/NIAMS. Grant Number: AR50627
- craniometaphyseal dysplasia;
- deletion mutation;
- intracellular protein trafficking
Craniometaphyseal dysplasia is caused by mutations in ANKH (ankylosis, progressive homolog [mouse]) in the majority of cases, and all of the reported mutations are single amino acid changes. Genomic DNA from an affected patient, his biological parents, and a sibling was amplified and ANKH was sequenced. The affected patient had a complex heterozygous mutation in exon 7 (c.936T > C, c.938C > G, c.942_953delTGGTTGACGGAA), predicting p.Try290Gln and p.Trp292_Glu295del. We studied the effect of the predicted mutation on the subcellular distribution of ANKH protein. Immunofluorescent labeling of COS-7 cells transduced with normal or mutant Ank (murine progressive ankylosis), showed that normal Ank localized to both the plasma membrane and cytoplasm, whereas mutant Ank was detected only in the cytoplasmic compartment. We propose that this craniometaphyseal dysplasia mutation causes a loss of ANKH protein expression and activity in the plasma membrane as a result of aberrant intracellular protein trafficking. © 2010 Wiley-Liss, Inc.