Sequence Analysis of PAX9, MSX1 and AXIN2 Genes in a Chinese

a r c h i v e s o f o r a l b i o l o g y 5 6 ( 2 0 1 1 ) 1 0 2 7 – 1 0 3 4

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Sequence analysis of PAX9, MSX1 and AXIN2 genes in

a Chinese oligodontia family

a a a b c d

Jing Wang , Fan Jian , Jing Chen , Hu Wang , Yunfeng Lin , Zhi Yang ,

e a,

Xiongfei Pan , Wenli Lai *

State Key Laboratory of Oral Diseases, Department of Orthodontics, West China College of Stomatology, Sichuan University, Chengdu,

Sichuan Province, PR China

State Key Laboratory of Oral Diseases, Department of Radiology, West China College of Stomatology, Sichuan University, Chengdu 610041,

Sichuan Province, PR China

State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Sichuan Province, PR China

Joint Orthodontics-Orthognathic Surgery Center, Shanghai 9th Hospital, Shanghai Jiaotong University, Shanghai, PR China

Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu 610041, PR China

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: The goal of our research was to look into the clinical traits and genetic mutations

Accepted 30 March 2011 in nonsyndromic oligodontia in a Chinese family and to gain insight into the role of

mutations of PAX9, MSX1 and AXIN2 in oligodontia phenotypes.

Keywords: Materials and methods: 6 subjects from a family underwent complete oral examination,

Oligodontia including panoramic radiographs. Retrospective data were reviewed and blood samples

PAX9 were collected. PCR primers for PAX9, MSX1, and AXIN2 were designed through the Oligo

MSX1 Primer Analysis Software. PCR products were puriﬁed and sequenced using the BigDye

AXIN2 Terminator Kit and analysed by the 3730 DNA Analyzer.

Phenotype Results: The proband missed 4 permanent canines, 2 permanent maxillary lateral incisors, 2

Genotype permanent mandibular lateral incisors, and 2 permanent mandibular central incisors,

whilst his maternal grandfather lacked only 2 permanent mandibular central incisors.

Single nucleotide polymorphism

Moreover, the size of some permanent teeth appeared smaller than normal values of crown

Missense mutation

width of Chinese people. Oligodontia and abnormalities of teeth were not present in other

family members. Radiographic examination showed that the proband and the rest of family

members retained all germs of the third molars. There was one known mutation A240P

(rs4904210) of PAX9 in the coding region in the proband and the maternal family members

(II-2, II-3, and II-4), which possibly contributed to structural and functional changes of

proteins. No mutations were identiﬁed in MSX1 and AXIN2.

Conclusions: Our ﬁndings may imply that the PAX9 A240P mutation is a risk factor for

oligodontia in the Chinese population. A240P is likely to be a genetic cause of oligodontia

though previous literature suggested it as a polymorphism only.

1. Introduction

absence of six or more permanent teeth, excluding third

molar. It is generally accepted that tooth development is

Congenitally missing teeth are common anomalies in human under strict genetic control. Previous studies show that PAX9,

tooth development. Oligodontia is deﬁned as congenital MSX1 and AXIN2 play a critical role in early tooth develop-

* Corresponding author at: State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology,

Sichuan University, No. 14, Section 3, Ren Min Nan Road, Chengdu, China. Tel.: +86 28 85501442; fax: +86 28 85582167.

E-mail addresses: [email protected], [email protected] (W. Lai).

1028 a r c h i v e s o f o r a l b i o l o g y 5 6 ( 2 0 1 1 ) 1 0 2 7 – 1 0 3 4

Table 1 – PAX9 mutations associated with non-syndromic oligodontia.

Exon Type of mutation Nucleotide change Amino acid change Tooth position involvement References

1 Missense A1G M1V Molars and premolars involved Klein et al.

2 Deletion/insertion/ 619_621delATCins- at aa 210 or 314 Molars dominating; premolars Mostowska et al.

duplication TACCGACCAAGGT- and incisors involved AGGGCATCCCT

2 Nonsense A340T L114X Molar and premolar dominating Nieminen et al.

2 Frameshift 219insG G73fsX316 Premolars and anterior teeth involved Stockton et al.

2 Missense G83C R28P Molars dominating Jumlongras et al.

a 13

2 N/A T62C L21P Molars dominating Das et al.

a 33

2 N/A T62C L21P Posterior tooth agenesis Kapadia H et al.

a 13

2 N/A A271G L91G Molars dominating Das et al.

2 Missense C76T A26T Molars dominating Lanmmi et al.

2 Missense G151A G51S Molars dominating Mostowska et al.

2 Missense C139T R47W Molars dominating Zhao et al.

a a 32

2 N/A C175T N/A Molars and premolars dominating Tallom-WaitonV et al.

2 Nonsense C433T Q145X Molars dominating, premolars involved Hansen et al.

2 Missense A259T I87P Posterior tooth agenesis Kapadia et al.

a 36

2 Frameshift 109insG N/A Molars dominating Zhao et al.

3 Missense G718C A240P Molar and premolar dominating, Nieminen et al.

Anterior teeth involved

3 Missense G718C A240P Molar and premolar dominating, Pawlowska et al.

Anterior teeth involved

3 Missense G718C A240P Anterior teeth involved Pan et al.

3 Missense G718C A240P Isolated anterior teeth involved Current study

4 Insertion 793insC A264fsX315 Molars dominating Frazier-Bower et al.

2 Missense G128A and C129A S43K Molars dominating Wang et al.

Deletion Heterozygous Deletion Molars dominating Das et al.

No specific information available.

2–7

ment. PAX9 (OMIM 167416), as a paired domain transcrip- molars, lower incisors, and upper lateral incisors. To date,

tion factor, has an important function in craniofacial 18 cases of nonsyndromic autosomal-dominant inherited

development. It is thought to be associated with human oligodontia associated with PAX9 mutations have been

8–21 2,8–17,20,31–36

oligodontia in various studies. MSX1 (OMIM 142983) is reported in literature (Table 1). Some studies have

essential for the switch in establishment of odontogenic suggested the MSX1 and AXIN2 mutations are associated with

22 4,7,25,37–39

potential of the mesenchyme. Mutations in MSX1 cause tooth agenesis as summarized in Table 2 and Table

28,40

tooth agenesis of various types of teeth, preferentially second 3. In the current research we investigated mutations in

8,17,23–25

premolars and incisors. Mutations in either PAX9 or three candidate genes PAX9, MSX1, and AXIN2 a Chinese

MSX1 can lead to defective protein–protein interactions for family of nonsyndromic oligodontia. 19,24

tooth morphogenesis.

AXIN2 (OMIM 604425) is known as an intracellular antago-

nist of Wnt signalling that is expressed in the dental 2. Material and methods

mesenchyme, odontoblasts and enamel knots. It is a

negative feedback regulator of Wnt-signalling by inducing 2.1. Patients

26–28

degradation of b-catenin. In humans, mutations in AXIN2

18,29

cause colorectal cancer and tooth agenesis that affects The male proband was referred to the Department of

permanent teeth predominantly, including permanent Orthodontics, West China Hospital of Stomatology, Sichuan

Table 2 – MSX1 mutations associated with non-syndromic oligodontia.

Region Type of Nucleotide Amino acid Tooth position involvement References mutation change change

Exon1 Frameshift 62G-duplication G22RfsX168 Premolars and mandibular incisors dominating. Kim et al.

Exon1 Transversion T182A Met61Lys Second premolars and third molars and incisors involved Lidral et al.

Exon2 Missense G587C Arg196Pro Second premolars and third molars and incisors involved Vastardis et al.

Exon2 Heterozygous C581T Ala194Val Molars and premolars dominating; incisors involved Mostowska et al.

Exon2 Missense C662A Ala221Glu Molars and premolars dominating; incisors involved Xuan et al.

Exon2 Transversion C559T Gln187Stop Second premolars and molars and incisors involved De Muynck et al.

Exon2 Missense G655A A219T Molars and premolars dominating; incisors involved Chishti et al. Download English Version: https://daneshyari.com/en/article/6051336

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