Mutations in MSX1, PAX9 and MMP20 genes in Saudi Arabian patients with tooth agenesis.

Tooth agenesis in human being is the most common congenital anomaly associated with dental development. Mutations in many genes such as MSH homeobox 1 (MSX1), paired box gene 9 (PAX9), ectodysplasin A (EDA) and EDA receptor (EDAR) have been associated with familial form of this condition. However, in large majority of patients, genetic cause could not be identified. The primary aim of present study was to identify the causative mutation(s) in these genes in Saudi Arabian families diagnosed with non-syndromic form of disease. Direct sequencing of coding regions, including exon-intron boundaries of these genes was carried out. All identified nucleotide variations were also tested to exclude possibility of being rare polymorphisms. The sequence analysis of exons and exon-intronic regions of these genes revealed five new mutations that include four in MSX1, one in PAX9 and one single nucleotide polymorphism (SNP) in majority of the patients in MMP20. One novel mutation in exon 1 of MSX1 gene (5354C > G; A40G) was found in three patients. In addition, another novel mutation was detected in two patients in exon 3 (PAX9) as g.10672A > T which changes asparagine to isoleucine at position 40. These mutations were not found in any of the control subjects. A single SNP in MMP20 genes (g.5066A > C) that changes lysine to threonine at position 18 was found in 10% controls as well. Our results for the first time demonstrates that mutations in MSX1 gene might play an important role in hypodontia cases involving pre-molars and is a risk factor for this ethnic population mainly of Arabs and is first report linking these mutations with tooth agenesis.

Shahid M ，Balto HA ，Al-Hammad N ，Joshi S ，Khalil HS ，Somily AM ，Sinjilawi NA ，Al-Ghamdi S ，Faiyaz-Ul-Haque M ，Dhillon VS ... -  《-》

Novel PAX9 mutation associated with syndromic tooth agenesis.

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 (MSX1), paired box 9 (PAX9), ectodysplasin A (EDA), and wingless-type MMTV integration site family, member 10 (WNT10A) 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.59delC mutation, segregating in the autosomal-dominant model, was identified in the PAX9 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 MSX1, EDA, and WNT10A genes. In conclusion, the novel PAX9 deletion might be responsible for tooth agenesis and trichodysplasia in the investigated family. This c.59delC mutation potentially leads to PAX9 transcription factor haploinsufficiency.

Mostowska A ，Zadurska M ，Rakowska A ，Lianeri M ，Jagodziński PP ... -  《-》

Mutation analysis by direct and whole exome sequencing in familial and sporadic tooth agenesis.

Salvi A ，Giacopuzzi E ，Bardellini E ，Amadori F ，Ferrari L ，De Petro G ，Borsani G ，Majorana A ... -  《-》

A screen of a large Czech cohort of oligodontia patients implicates a novel mutation in the PAX9 gene.

Tooth agenesis is one of the most common developmental anomalies in humans. To date, many mutations involving paired box 9 (PAX9), msh homeobox 1 (MSX1), and axin 2 (AXIN2) genes have been identified. The aim of the present study was to perform screening for mutations and/or polymorphisms using the capillary sequencing method in the critical regions of PAX9 and MSX1 genes in a group of 270 individuals with tooth agenesis and in 30 healthy subjects of Czech origin. This screening revealed a previously unknown heterozygous g.9527G>T mutation in the PAX9 gene in monozygotic twins with oligodontia and three additional affected family members. The same variant was not found in healthy relatives. This mutation is located in intron 2, in the region recognized as the splice site between exon 2 and intron 2. We hypothesize that the error in pre-mRNA splicing may lead to lower expression of PAX9 protein and could have contributed to the development of tooth agenesis in the affected subjects.

Šerý O ，Bonczek O ，Hloušková A ，Černochová P ，Vaněk J ，Míšek I ，Krejčí P ，Izakovičová Hollá L ... -  《-》

Effects of PAX9 and MSX1 gene variants to hypodontia, tooth size and the type of congenitally missing teeth.

Kirac D ，Eraydin F ，Avcilar T ，Ulucan K ，Özdemir F ，Guney AI ，Kaspar EÇ ，Keshi E ，Isbir T ... -  《-》