Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK

Ernst Reichenberger, Valdenize Tiziani, Shoji Watanabe, Lucy Park, Yasuyoshi Ueki, Carla Santanna, Scott T. Baur, Rita Shiang, Dorothy K. Grange, Peter Beighton, Jessica Gardner, Herman Hamersma, Sean Sellars, Rajkumar Ramesar, Andrew C. Lidral, Annmarie Sommer, Cassio M. Raposo do Amaral, Robert J. Gorlin, John B. Mulliken, Bjorn R. Olsen

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

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 ∼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.

Original languageEnglish (US)
Pages (from-to)1321-1326
Number of pages6
JournalAmerican Journal of Human Genetics
Volume68
Issue number6
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Mutation
Bone Matrix
Proteins
Genetic Association Studies
Bone Density
Genetic Recombination
Extracellular Matrix
Chromosomes
Amino Acids
Bone and Bones
Autosomal Dominant Craniometaphyseal Dysplasia
diphosphoric acid
Schwartz-Lelek syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. / Reichenberger, Ernst; Tiziani, Valdenize; Watanabe, Shoji; Park, Lucy; Ueki, Yasuyoshi; Santanna, Carla; Baur, Scott T.; Shiang, Rita; Grange, Dorothy K.; Beighton, Peter; Gardner, Jessica; Hamersma, Herman; Sellars, Sean; Ramesar, Rajkumar; Lidral, Andrew C.; Sommer, Annmarie; Raposo do Amaral, Cassio M.; Gorlin, Robert J.; Mulliken, John B.; Olsen, Bjorn R.

In: American Journal of Human Genetics, Vol. 68, No. 6, 01.01.2001, p. 1321-1326.

Research output: Contribution to journalArticle

Reichenberger, E, 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 2001, 'Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK', American Journal of Human Genetics, vol. 68, no. 6, pp. 1321-1326. https://doi.org/10.1086/320612
Reichenberger, Ernst ; Tiziani, Valdenize ; Watanabe, Shoji ; Park, Lucy ; Ueki, Yasuyoshi ; Santanna, Carla ; Baur, Scott T. ; Shiang, Rita ; Grange, Dorothy K. ; Beighton, Peter ; Gardner, Jessica ; Hamersma, Herman ; Sellars, Sean ; Ramesar, Rajkumar ; Lidral, Andrew C. ; Sommer, Annmarie ; Raposo do Amaral, Cassio M. ; Gorlin, Robert J. ; Mulliken, John B. ; Olsen, Bjorn R. / Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. In: American Journal of Human Genetics. 2001 ; Vol. 68, No. 6. pp. 1321-1326.
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AU - Santanna, Carla

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AU - Sommer, Annmarie

AU - Raposo do Amaral, Cassio M.

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AU - Mulliken, John B.

AU - Olsen, Bjorn R.

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