Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta.

Abstract

A combination of autozygosity mapping and exome sequencing identified a null mutation in SLC24A4 in a family with hypomineralized amelogenesis imperfect a (AI), a condition in which tooth enamel formation fails. SLC24A4 encodes a calcium transporter upregulated in ameloblasts during the maturation stage of amelogenesis. Screening of further AI families identified a missense mutation in the ion-binding site of SLC24A4 expected to severely diminish or abolish the ion transport function of the protein. Furthermore, examination of previously generated Slc24a4 null mice identified a severe defect in tooth enamel that reflects impaired amelogenesis. These findings support a key role for SLC24A4 in calcium transport during enamel formation.

• Authors: David A Parry, James A Poulter, Clare V Logan, Steven J Brookes, Hussain Jafri, Christopher H Ferguson, Babra M Anwari, Yasmin Rashid, Haiqing Zhao, Colin A Johnson, Chris F Inglehearn, Alan J Mighell
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 92 Issue 2 Pg. 307-12 (Feb 07 2013) ISSN: 1537-6605 [Electronic] United States
• PMID: 23375655 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiporters
• SLC24A4 protein, human
• Slc24a4 protein, mouse
• Sodium-Calcium Exchanger
• potassium-dependent sodium-calcium exchanger

Topics

• Amelogenesis Imperfecta (genetics)
• Amino Acid Sequence
• Animals
• Antiporters (chemistry, genetics)
• Base Sequence
• Family
• Female
• Humans
• Incisor (ultrastructure)
• Male
• Mice
• Mice, Knockout
• Molecular Sequence Data
• Mutation (genetics)
• Pedigree
• Phenotype
• Sodium-Calcium Exchanger (genetics)