title: Single median maxillary central incisor: new data and mutation review.
abstract: BACKGROUND
  Single median maxillary central incisor (SMMCI) is a rare anomaly that may occur alone or associated with other conditions, frequently as part of the holoprosencephaly (HPE) spectrum. However, it has been suggested that SMMCI alone, or associated with some midline defects, may be considered a different entity from HPE (OMIM: 147250). Families with SMMCI, without HPE cases, are difficult to counsel for the risk of HPE in future generations because the same midline defects described as part of the "SMMCI syndrome" can also be part of the HPE spectrum.
  
  
  METHODS
  We screened five cases of SMMCI for mutations in three HPE genes, SHH, TGIF, and SIX3.
  
  
  RESULTS
  A missense mutation c.686C>T was found in the gene SIX3 of one patient, which did not differ from the accepted 20% of known HPE gene mutations among all HPE cases. Our results and an extensive literature review of gene mutations in patients with SMMCI showed that 27/28 of them were in HPE genes: SHH (n = 21), SIX3 (n = 3), TGIF (n = 1), GLI2 (n = 1), and PTCH (n = 1), and only one in the SALL4 gene.
  
  
  CONCLUSIONS
  The clinical findings in patients with SMMCI without HPE in families with mutations in HPE genes cannot be distinguished from the findings reported in the SMMCI syndrome. Therefore, persons with SMMCI and their relatives should be carefully investigated for related midline disorders, especially of the HPE spectrum, and all known HPE genes screened.
authors.affiliation: Estudo Latino Americano de Malformações Congênitas, Departamento de Genética, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Kênia B
authors.initials: KB
authors.lastname: El-Jaick
authors.forename: Renata F
authors.initials: RF
authors.lastname: Fonseca
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Moreira
authors.forename: Márcia G
authors.initials: MG
authors.lastname: Ribeiro
authors.forename: Ana M
authors.initials: AM
authors.lastname: Bolognese
authors.forename: Sânia O
authors.initials: SO
authors.lastname: Dias
authors.forename: Eliane T
authors.initials: ET
authors.lastname: Pereira
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.forename: Iêda M
authors.initials: IM
authors.lastname: Orioli
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D002648:Child; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007180:Incisor / Q000002:abnormalities*; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000097607:Homeobox Protein SIX3