| Autor: |
Reichenberger E; Harvard-Forsyth Department of Oral Biology, The Forsyth Institute, Harvard School of Dental Medicine, and Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Ernst_Reichenberger@hms.harvard.edu, Tiziani V, Watanabe S, Park L, Ueki Y, Santanna C, Baur ST, Shiang R, Grange DK, Beighton P, Gardner J, Hamersma H, Sellars S, Ramesar R, Lidral AC, Sommer A, Raposo do Amaral CM, Gorlin RJ, Mulliken JB, Olsen BR |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of human genetics [Am J Hum Genet] 2001 Jun; Vol. 68 (6), pp. 1321-6. Date of Electronic Publication: 2001 Apr 16. |
| DOI: |
10.1086/320612 |
| Abstrakt: |
Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in long bones. Linkage studies mapped the locus for the autosomal dominant form of CMD to an approximately 5-cM interval on chromosome 5p, which is defined by recombinations between loci D5S810 and D5S1954. Mutational analysis of positional candidate genes was performed, and we describe herein three different mutations, in five different families and in isolated cases, in ANK, a multipass transmembrane protein involved in the transport of intracellular pyrophosphate into extracellular matrix. The mutations are two in-frame deletions and one in-frame insertion caused by a splicing defect. All mutations cluster within seven amino acids in one of the six possible cytosolic domains of ANK. These results suggest that the mutated protein has a dominant negative effect on the function of ANK, since reduced levels of pyrophosphate in bone matrix are known to increase mineralization. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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