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Novel PAX 9 mutation associated with syndromic tooth agenesis
Author(s) -
Mostowska Adrianna,
Zadurska Małgorzata,
Rakowska Adriana,
Lianeri Margarita,
Jagodziński Paweł P.
Publication year - 2013
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12071
Subject(s) - haploinsufficiency , genetics , frameshift mutation , proband , biology , exon , mutation , hypodontia , gene , homeobox , transcription factor , medicine , phenotype , dentistry
Tooth agenesis is the most common anomaly of dental development. The purpose of the present study was to identify the causative mutation(s) in a family with a syndromic form of hypodontia. The male proband lacked 19 permanent teeth and showed defects of hair, but lacked ectodermal symptoms of skin and nails. Direct sequencing of the coding regions, including exon/intron boundaries of the msh homeobox 1 ( MSX 1 ), paired box 9 ( PAX 9 ), ectodysplasin A ( EDA ), and wingless‐type MMTV integration site family, member 10 ( WNT 10A ) genes, was carried out in affected family members. All identified nucleotide variations were tested in 200 healthy individuals using high‐resolution melting ( HRM ) curve analysis to exclude the possibility that they represent rare polymorphisms. A novel heterozygous c.59del C mutation, segregating in the autosomal‐dominant model, was identified in the PAX 9 gene of the proband and the family members studied. This one‐nucleotide deletion, located in a highly conserved paired box sequence, resulted in a frameshift (p.Pro20Argfs65) and in premature termination of translation, yielding a truncated protein 258 amino acids shorter than the wildtype protein. No pathogenic mutations were found in the MSX 1 , EDA , and WNT 10 A genes. In conclusion, the novel PAX 9 deletion might be responsible for tooth agenesis and trichodysplasia in the investigated family. This c.59delC mutation potentially leads to PAX 9 transcription factor haploinsufficiency.