title: Non-syndromic severe hypodontia caused by a novel frameshift insertion mutation in the homeobox of the MSX1 gene.
abstract: OBJECTIVE
  Inherited congenital anomalies in tooth number, particularly hypodontia are relatively common. Although substantial progress has been made that permits a better understanding of the causes of tooth agenesis, overall knowledge of the phenotype:genotype correlations in this anomaly are still lacking. The aim in this study was to identify the causal gene mutation(s) in a family of two sisters with severe hypodontia (oligodontia) including 2nd premolars and 1st and 3rd molars, using whole exome sequencing (WES).
  
  
  METHODS
  WES was performed using in-solution hybridization, followed by massively parallel sequencing.
  
  
  RESULTS
  A frameshift insertion of 7 basepairs (GCAAGTT) in the homebox of MSX1 gene located in the exon 2 in heterozygous state has been identified in both sisters (NM_002448:exon2:c.572_573ins GCAAGTT: p.F191fs).
  
  
  CONCLUSIONS
  We conclude that this frameshift mutation in the homeodomain (which plays an essential role in DNA binding) of MSX1 gene is responsible for tooth agenesis in this family. This expands the phenotype-genotype correlation associated with MSX1 mutations.
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London, London, SE1 9RT, UK; College of Dentistry, University of Baghdad. Electronic address: Mushriq.abid@kcl.ac.uk.
authors.forename: Mushriq F
authors.initials: MF
authors.lastname: Abid
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, SE1 9RT, UK. Electronic address: Michael.simpson@kcl.ac.uk.
authors.forename: M A
authors.initials: MA
authors.lastname: Simpson
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, SE1 9RT, UK. Electronic address: christos.petridis@kcl.ac.uk.
authors.forename: Christos
authors.initials: C
authors.lastname: Petridis
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London, London, SE1 9RT, UK. Electronic address: Martyn.coboune@kcl.ac.uk.
authors.forename: M T
authors.initials: MT
authors.lastname: Cobourne
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London, London, SE1 9RT, UK. Electronic address: paul.sharpe@kcl.ac.uk.
authors.forename: P T
authors.initials: PT
authors.lastname: Sharpe
mesh_terms: D000328:Adult; D000848:Anodontia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D001641:Bicuspid / Q000002:abnormalities / Q000000981:diagnostic imaging; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005801:Genes, Homeobox; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics* / Q000502:physiology; D008963:Molar / Q000002:abnormalities / Q000000981:diagnostic imaging; D016254:Mutagenesis, Insertional; D011862:Radiography, Panoramic; D000073359:Exome Sequencing
chemical_list: D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human
keywords: Exome sequencing; Frameshift; MSX1