Mutations in C4orf26, Encoding a Peptide with In Vitro Hydroxyapatite Crystal Nucleation and Growth Activity, Cause Amelogenesis Imperfecta

• Published in: American journal of human genetics Vol. 91; no. 3; pp. 565 - 571
• Main Authors: Parry, David A., Brookes, Steven J., Logan, Clare V., Poulter, James A., El-Sayed, Walid, Al-Bahlani, Suhaila, Al Harasi, Sharifa, Sayed, Jihad, Raïf, El Mostafa, Shore, Roger C., Dashash, Mayssoon, Barron, Martin, Morgan, Joanne E., Carr, Ian M., Taylor, Graham R., Johnson, Colin A., Aldred, Michael J., Dixon, Michael J., Wright, J. Tim, Kirkham, Jennifer, Inglehearn, Chris F., Mighell, Alan J.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 07.09.2012; Cell Press; Elsevier
• Subjects: Amelogenesis - genetics; Amelogenesis Imperfecta - genetics; Biological and medical sciences; Cells; Dental Enamel - metabolism; Durapatite - metabolism; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Genetics of eukaryotes. Biological and molecular evolution; Humans; Male; Medical disorders; Medical genetics; Medical sciences; Molecular and cellular biology; Mutation; Nerve Tissue Proteins - genetics; Non tumoral diseases; Otorhinolaryngology. Stomatology; Pedigree; Peptides; Proteins; Teeth; Peptides; Stomatology; Growth; Dental disease; Activity; Genetics; Hydroxyapatite; Mutation; Amelogenesis imperfecta; In vitro; Dental dysplasia; Genetic disease
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2012.07.020

Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein’s phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.