Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.
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.
Leeds Institute of Molecular Medicine, St. James's University Hospital, University of Leeds, LS9 7TF Leeds, UK.
David A
DA
Parry
Steven J
SJ
Brookes
Clare V
CV
Logan
James A
JA
Poulter
Walid
W
El-Sayed
Suhaila
S
Al-Bahlani
Sharifa
S
Al Harasi
Jihad
J
Sayed
El Mostafa
el M
Raïf
Roger C
RC
Shore
Mayssoon
M
Dashash
Martin
M
Barron
Joanne E
JE
Morgan
Ian M
IM
Carr
Graham R
GR
Taylor
Colin A
CA
Johnson
Michael J
MJ
Aldred
Michael J
MJ
Dixon
J Tim
JT
Wright
Jennifer
J
Kirkham
Chris F
CF
Inglehearn
Alan J
AJ
Mighell
D000566:Amelogenesis / Q000235:genetics; D000567:Amelogenesis Imperfecta / Q000235:genetics*; D003743:Dental Enamel / Q000378:metabolism; D017886:Durapatite / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree
C560924:C4ORF48 protein, human; D009419:Nerve Tissue Proteins; D017886:Durapatite