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A novel PITX2 mutation in non‐syndromic orodental anomalies
Author(s) -
Intarak N,
Theerapa T,
Ittiwut C,
Suphapeetiporn K,
Porntaveetus T,
Shotelersuk V
Publication year - 2018
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12804
Subject(s) - sanger sequencing , frameshift mutation , genetics , proband , exome sequencing , hypodontia , anodontia , mutation , oligodontia , medicine , dens invaginatus , biology , transcription activator like effector nuclease , gene , dentistry , genome , genome editing , invagination
Objective To identify orodental characteristics and genetic aetiology of a family affected with non‐syndromic orodental anomalies. Subjects and Methods Physical and oral features were characterised. DNA was collected from an affected Thai family. Whole‐exome sequencing was employed to identify the pathogenic variants associated with inherited orodental anomalies. The presence of the identified mutation was confirmed by Sanger sequencing. Results We observed unique orodental manifestations including oligodontia, retained primary teeth, taurodont molars, peg‐shaped maxillary central incisors, high attached frenum with nodule and midline diastema in the proband and her mother. Mutation analyses revealed a novel heterozygous frameshift deletion, c.573_574delCA, p.L193QfsX5, in exon 5 of PITX2A in affected family members. The amino acid alterations, localised in the transcriptional activation domain 2 in the C‐terminus of PITX2, were evolutionarily conserved. Mutations in PITX2 have been associated with autosomal‐dominant Axenfeld–Rieger syndrome and non‐syndromic eye abnormalities, but never been found to cause isolated oral anomalies. Conclusions This study for the first time demonstrates that the PITX2 mutation could lead to non‐syndromic orodental anomalies in humans. We propose that the specific location in the C‐terminal domain of PITX2 is exclusively necessary for tooth development.