PMID- 24858907
OWN - NLM
STAT- MEDLINE
DCOM- 20150603
LR  - 20220331
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 23
IP  - 20
DP  - 2014 Oct 15
TI  - Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.
PG  - 5317-24
LID - 10.1093/hmg/ddu247 [doi]
AB  - Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental 
      enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is 
      the second most abundant enamel matrix protein expressed during amelogenesis. The 
      pivotal role of AMBN in amelogenesis has been confirmed experimentally using 
      mouse models. However, no AMBN mutations have been associated with human AI. 
      Using autozygosity mapping and exome sequencing, we identified genomic deletion 
      of AMBN exon 6 in a second cousin consanguineous family with three of the six 
      children having hypoplastic AI. The genomic deletion corresponds to an in-frame 
      deletion of 79 amino acids, shortening the protein from 447 to 368 residues. 
      Exfoliated primary teeth (unmatched to genotype) were available from family 
      members. The most severely affected had thin, aprismatic enamel (similar to that 
      reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth 
      exhibited thicker but largely aprismatic enamel. One tooth had apparently normal 
      enamel. It has been suggested that AMBN may function in bone development. No 
      clinically obvious bone or other co-segregating health problems were identified 
      in the family investigated. This study confirms for the first time that AMBN 
      mutations cause non-syndromic human AI and that mouse models with disrupted Ambn 
      function are valid.
CI  - (c) The Author 2014. Published by Oxford University Press.
FAU - Poulter, James A
AU  - Poulter JA
AD  - Leeds Institute of Biomedical and Clinical Sciences, St James's University 
      Hospital, University of Leeds, Leeds LS9 7TF, UK.
FAU - Murillo, Gina
AU  - Murillo G
AD  - School of Dentistry and.
FAU - Brookes, Steven J
AU  - Brookes SJ
AD  - School of Dentistry, University of Leeds, Leeds LS2 9LU, UK.
FAU - Smith, Claire E L
AU  - Smith CE
AD  - Leeds Institute of Biomedical and Clinical Sciences, St James's University 
      Hospital, University of Leeds, Leeds LS9 7TF, UK.
FAU - Parry, David A
AU  - Parry DA
AD  - Leeds Institute of Biomedical and Clinical Sciences, St James's University 
      Hospital, University of Leeds, Leeds LS9 7TF, UK.
FAU - Silva, Sandra
AU  - Silva S
AD  - Biology, Molecular Cellular Centre (CBCM), University of Costa Rica, San Pedro, 
      Costa Rica.
FAU - Kirkham, Jennifer
AU  - Kirkham J
AD  - School of Dentistry, University of Leeds, Leeds LS2 9LU, UK.
FAU - Inglehearn, Chris F
AU  - Inglehearn CF
AD  - Leeds Institute of Biomedical and Clinical Sciences, St James's University 
      Hospital, University of Leeds, Leeds LS9 7TF, UK.
FAU - Mighell, Alan J
AU  - Mighell AJ
AD  - Leeds Institute of Biomedical and Clinical Sciences, St James's University 
      Hospital, University of Leeds, Leeds LS9 7TF, UK School of Dentistry, University 
      of Leeds, Leeds LS2 9LU, UK a.j.mighell@leeds.ac.uk.
LA  - eng
GR  - 093113/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140523
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (AMBN protein, human)
RN  - 0 (Dental Enamel Proteins)
SB  - IM
MH  - Amelogenesis Imperfecta/genetics/*pathology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Dental Enamel Proteins/*genetics
MH  - Exons
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Pedigree
MH  - Polymorphism, Single Nucleotide
MH  - Sequence Analysis, DNA
MH  - *Sequence Deletion
MH  - Tooth/pathology/*ultrastructure
PMC - PMC4168819
EDAT- 2014/05/27 06:00
MHDA- 2015/06/04 06:00
PMCR- 2014/05/23
CRDT- 2014/05/27 06:00
PHST- 2014/05/27 06:00 [entrez]
PHST- 2014/05/27 06:00 [pubmed]
PHST- 2015/06/04 06:00 [medline]
PHST- 2014/05/23 00:00 [pmc-release]
AID - ddu247 [pii]
AID - 10.1093/hmg/ddu247 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2014 Oct 15;23(20):5317-24. doi: 10.1093/hmg/ddu247. Epub 2014 May 
      23.