Archives of Oral Biology 61 (2016) 144–148

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Archives of Oral Biology

journal homepage: www.elsevier.com/locate/aob

A novel initiation codon mutation of PAX9 in a family with oligodontia

Jia Lianga,b,1, Chuanqi Qina,1, Haitang Yuea , Hong Hec,**, Zhuan Biana,*
a
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School
& Hospital of Stomatology, Wuhan University, Wuhan, China
b
Department Two of Endodontics, Hospital and School of Stomatology, Wuhan University, Wuhan, China
c
Department One of Orthodontics, Hospital and School of Stomatology, Wuhan University, Wuhan, China

A R T I C L E I N F O A B S T R A C T

Article history: Objective: Recent studies have attributed non-syndromic tooth agenesis to mutations in several genes,
Received 11 February 2015 including MSX1, PAX9, AXIN2, WNT10A and EDA. In this study, mutation of PAX9gene was investigated in a
Received in revised form 21 October 2015 four-generation Chinese family with oligodontia.
Accepted 25 October 2015
Design: Genomic DNA was isolated from the blood samples of all the available family members. Candidate
genes MSX1 and PAX9 were amplified using polymerase chain reaction and then directly sequenced.
Keywords: Results: A novel initiation codon mutation was identified; it consisted of a heterozygous c.2T > G mutation
Oligodontia
in the PAX9 gene which changed the ATG initiation codon to AGG. Restriction-enzyme analysis was
PAX9
Initiation codon
performed to verify this mutation, which was segregated amongst the members with the oligodontia
phenotype.
Conclusions: Our results demonstrate a new initiation codon mutation in the PAX9 gene. This mutation
probably caused the oligodontia in the investigated Chinese family through haplo-insufficiency.
ã 2015 Elsevier Ltd. All rights reserved.

1. Introduction
Tooth agenesis is a common developmental anomaly in
humans, which occurs in 3–10% of the population (De, Oster,
Marks, Martens, & Huysseune, 2009). Three terms are used to
describe tooth agenesis according to the number of missing teeth:
hypodontia is defined as absence of one to six permanent teeth,
excluding third molars; oligodontia refers to the absence of more
than six permanent teeth, excluding third molars; and anodontia
denotes the absence of all teeth (Schalk-van der Weide, Beemer,
Faber, & Bosman, 1994). Agenesis can also be classified into non-
syndromic and syndromic tooth agenesis according to the
accompanying symptoms (Vastardis, 2000). Any disturbance in
tooth development which involves a series of inductive inter-
actions between epithelium and underlying mesenchyme may
result in tooth agenesis or other dental defects (Thesleff, 2006).
Mutations in MSX1, PAX9, AXIN2, WNT10A and EDA have been
proven to cause non-syndromic tooth agenesis (Vastardis,
Karimbux, Guthua, Seidman, & Seidman, 1996; Stockton, Das,
* Corresponding author at: School & Hospital of Stomatology, Wuhan University,
237 Luoyu Road, Wuhan 430079, China.
** Corresponding author at: School & Hospital of Stomatology, Wuhan University,
237 Luoyu Road, Wuhan 430079, China.
E-mail addresses: drhehong@hotmail.com (H. He), bz@whuss.com (Z. Bian).
1
These authors contributed equally to this work.
Goldenberg, D’Souza, & Patel, 2000; Lammi et al., 2004; van den
Boogaard, Creton, Bronkhorst, van der Hout, Hennekam, &
Lindhout, 2012; Tao et al., 2006)
PAX9 is localised in chromosome 14(14q12–q13) and is a member
of the PAX gene family, which encodes a group of transcription
factors that are critical for foetal growth and organogenesis. PAX
proteins are defined by the presence of a DNA-binding domain (the
paired-domain), which makes sequence-specific contact with DNA
(Chi & Epstein, 2002). Pax9 is widely expressed in neural crest-
derived mesenchyme, which is involved in craniofacial and tooth
development (Peters, Neubuser, Kratochwil, & Balling, 1998).
Homozygous Pax9-deficient mice die shortly after birth, lack
pharyngeal pouch derivatives and exhibit numerous craniofacial
and limb anomalies. All mutant mice fail to form teeth beyond the
bud stage and have a cleft secondary palate. Heterozygous
Pax9 mutant mice do not exhibit any obvious abnormalities,
indicating that Pax9 is haploid sufficient (Peters et al., 1998). Since
the first discovery of PAX9 mutation (Stockton et al., 2000), a number
of autosomal dominant mutations ranging from in-frame to out-of-
frame mutations have been associated with this disorder. Most of
these mutations cluster in and around the paired-domain,
indicating that this region might be a mutation hotspot of PAX9.
In the present study, we describe a four-generation family in
which tooth agenesis is inherited in an autosomal dominant
manner. Mutational screening for candidate genes was performed
to associate genotype with phenotype.

http://dx.doi.org/10.1016/j.archoralbio.2015.10.022
0003-9969/ ã 2015 Elsevier Ltd. All rights reserved.
 J. Liang et al. / Archives of Oral Biology 61 (2016) 144–148 145

2. Materials and methods
2.1. Subjects
The study included subjects from a family of Chinese descent
who were referred to the orthodontic department at the School of
Stomatology, Wuhan University. Pedigree construction was con-
ducted by clinical examination and interview of the available
family members. Panoramic radiographs and photographs were
obtained to verify tooth agenesis. Blood samples were collected
from the available family members and 100 unrelated healthy
controls. The study was conducted with the informed consent of
the family members and approval of the Institutional Review
Board.
sequencing of exons and exon–intron boundaries of two genes,
namely, MSX1 (GenBank accession number M97676) and PAX9
(GenBank accession number AJ238381) as described previously
(Klein, Nieminen, Lammi, Niebuhr, & Kreiborg, 2005).
2.3. Restriction analysis
Genomic DNA of all the available family members was
amplified with specific primers PAX9initialF 50 -CCAGGTGGG-
GAGCTAGCCTG-30 and PAX9initialR 50 -AGTCAATAGAGAATGT-
GAGCGCCT-30 . The amplified fragments were then subjected to
restriction digestion with BsrDI (NEB) following the manufacturer’s
instructions. Digestion products were analyzed by agarose gel
electrophoresis.

2.2. Mutation detection 3. Results

Genomic DNA was extracted from the peripheral blood samples 3.1. Pedigree and phenotype analyses
of all the available members and controls following the standard
salt extraction procedure. Pathogenic mutations were screened Pedigree analysis indicated that oligodontia in this family was
using polymerase chain reaction (PCR) amplification and segregated in an autosomal dominant pattern (Fig. 1a). Oligodontia

Fig. 1. (a) Pedigree of the four-generation Chinese family with oligodontia. (b) Panoramic radiograph of the proband. The white star indicates missing permanent tooth. (c)
Clinical photograph of the proband; upper jaw and lower jaw. (d) Tooth phenotypes of the family members with oligodontia. $denotes congenitally missing tooth and
~denotes cone-shaped tooth.
146 J. Liang et al. / Archives of Oral Biology 61 (2016) 144–148
could be traced back to four generations in this family. Nine family
members are involved in this study, and seven of them could be
diagnosed with oligodontia based on panoramic radiographs and
photographs (Fig. 1b and c). The proband, a 12-year-old boy,
together with his relatives, lacked most of their permanent molars.
Most individuals also lacked maxillary second premolars and
incisors. Moreover, some individuals lacked at least one of their
canines, indicating that the pattern of missing teeth involved all
classes of teeth. Some patients were reported to have cone-shaped
teeth (Fig. 1d). IV4 and IV10 were reported to have normal primary
dentition, the status of which was not available for other
individuals. Given that several extractions were performed to
accommodate prostheses, we could not ascertain the exact
number or types of missing II1 and II3 teeth. III2 and II2 were
not available for clinical examination; their phenotypes were
obtained based on the interview of available family members. The
members had no other ectodermal abnormalities in the sweat
glands, hair or nails, and their clinical findings did not suggest the
presence of any syndrome or systemic disorder.
3.2. Mutation analysis
A heterozygous c.2T > G mutation was detected in exon 1 of PAX9
in all available affected individuals (Fig. 2a). This c.2T > G trans-
version changed the ATG initiation codon to AGG. In addition,
sequencing of MSX1 and other exons of PAX9 did not show mutation
in any of the affected individuals. The mutation was not detected in
any of the unaffected relatives and the 100 controls (data not
shown). The single base change of a T to a G destroys a BsrDI
restriction site. Thus, we performed restriction-enzyme analysis.
The DNA of all available family members was amplified with the
Fig. 2. (a) Chromatogram showing the c.2T > G mutation, which changes the
initiation codon from ATG to AGG. WT indicates wild type. (b) Restriction-enzyme
analysis of PCR-amplified DNA fragments around the initiation codon of PAX9. The
mutation destroyed the cleavage site for BsrDI. The PCR fragments (517 bp) were
digested with BsrDI. The mutant allele was not cleaved at this site (longer fragment),
whereas the WT was cleaved normally (shorter fragment).
specific primers. The PCR products were digested with BsrDI and
analyzed using 3% agarose gel electrophoresis. The presence of the
mutation in the affected family member was confirmed (Fig. 2b).
4. Discussion
Several genes, including MSX1, PAX9, AXIN2, WNT10AandEDA,
have been involved in non-syndromic tooth agenesis. MSX1
mutations cause second premolar agenesis, whereas PAX9
mutations cause molar agenesis (Kim, Simmer, Lin, & Hu, 2006).
AXIN2-associated tooth agenesis is often accompanied with
predisposing to colorectal cancer (Lammi et al., 2004). In addition,
EDA mutations are more likely to cause anterior teeth agenesis
(Han et al., 2008), whereas WNT10A aberrations usually cause
autosomal recessive or isolated tooth agenesis (van den Boogaard
et al., 2012). In this four-generation oligodontia family, the pattern
of missing teeth involved all classes of teeth. Therefore, we selected
MSX1 and PAX9 prior to the other candidate genes.
To date, about thirty PAX9 mutations have been found (Stockton
et al., 2000; van den Boogaard et al., 2012; Klein et al., 2005; Wang
et al., 2009a; Wang, Chan, Makovey, Simmer, & Hu, 2012; Das et al.,
2003; Mitsui et al., 2014; Lammi et al., 2003; Liang, Song, Li, & Bian,
2012; Jumlongras et al., 2004; Zhao et al., 2007; Mostowska,
Kobielak, Biedziak, & Trzeciak, 2003; Bergendal, Klar, Stecksen-
Blicks, Norderyd, & Dahl, 2011; Kapadia, Frazier-Bowers, Ogawa, &
D’Souza, 2006; Tallon-Walton et al., 2007; Nieminen et al., 2001;
Hansen, Kreiborg, Jarlov, Niebuhr, & Eiberg, 2007; Zhu, Yang,
Zhang, Ge, & Zheng, 2012; Mostowska, Zadurska, Rakowska,
Lianeri, & Jagodzinski, 2013a; Suda, Ogawa, Kojima, Saito, &
Moriyama, 2011; Mostowska, Biedziak, & Trzeciak, 2006; Frazier-
Bowers et al., 2002; Mostowska et al., 2013b; Das et al., 2002)
(Table 1). And we differentiated all these mutations into two
subsets (Zhong et al., 2009). The first subset, in-frame mutations,
includes missense mutations and in-frame insertions or deletions.
The second subset, truncating mutations, includes nonsense
mutations, out-of-frame insertions or deletions, initiation codon
mutations and deletion of the entire gene. The phenotypes caused
by truncating mutations are more severe than those caused by in-
frame mutations (Fig. 3): first, the average tooth missing number in
truncating mutations subset is a little larger than that in in-frame
mutations subset; second, primary tooth agenesis only appeared in
truncating mutations subset. Combined with other functional
studies of PAX9 (Liang et al., 2012; Suda et al., 2011; Wang et al.,
2009b), we suggest that truncating mutations have a more serious
effect on PAX9 protein than in-frame mutations and
PAX9 mutations cause tooth agenesis as a dose-sensitive manner.
In the present study, we report a second initiation codon
mutation of PAX9, c.2T > G, which is associated with non-
syndromic oligodontia. The mutation is present in all affected
family members, whereas all unaffected family members and
100 controls are negative for this mutation. The first initiation
codon mutation of PAX9, c.1A > G (Klein et al., 2005), was also
associated with non-syndromic oligodontia in the family of
Chinese decent. Some similarities of the phenotypes were found
in the two families. Tooth agenesis was severe and affected all
types of teeth, particularly the permanent molars, which
correlated well with reports on PAX9 mutation families. Peg-
shaped teeth were found in patients of both families. By contrast,
the primary teeth in this family were not affected. This difference
may be attributed to phenotypic heterogeneity and to the
availability of only two patients for primary agenesis evaluation.
In this study, the mutation was found to change a methionine
codon at position 1 to an arginine. We hypothesised that such
change might lead to a low level of initiation of mRNA translation
from the mutated allele. The scanning mechanism for the
translation initiation proposes that the ribosome normally scans
 J. Liang et al. / Archives of Oral Biology 61 (2016) 144–148 147

Table 1
Two subsets of PAX9 mutations.

Type of mutation *Nucleotide change *Effect Paired domain Total missing Number of patients References
protein affected number
In-frame mutation
Missense c.16G > A p.G6R Yes 3 1 Wang et al. (2009a)
Missense c.43T > A p.F15I Yes 14 2 Wang et al. (2012)
Missense c.62T > C p.L21P Yes 91 9 Das et al. (2003)
Del c.73–75 del ATC p.I25del Yes 6 1 Mitsui et al. (2014)
Missense c.76C > T p.R26W Yes 45 4 Lammi et al. (2003)
Missense c.80T > C p.L27P Yes 19 2 Liang et al. (2012)
Missense c.83G > C p.R28P Yes 13 1 Jumlongras et al. (2004)
Missense c.86T > C p.I29T Yes 20 2 Liang et al. (2012)
Missense c.128G > A; p.S43K Yes 13 2 Wang et al. (2009a)
c.129C > A
Missense c.139C > T p.R47W Yes 16 1 Zhao et al. (2007)
Missense c.146C > T p.S49L Yes 10 1 Mitsui et al. (2014)
Missense c.151G > A p.G51S Yes 9 1 Mostowska et al. (2003)
Missense c.152G > C p.G51A Yes 7 1 Bergendal et al. (2011)
Missense c.238A > G p.T80A Yes 8 1 Bergendal et al. (2011)
Missense c.259A > T p.I87F Yes 23 2 Kapadia et al. (2006)
Missense c.271A > G p.K91E Yes 44 6 Das et al. (2003)
Missense c.428A > G p.Y143C No 11 1 Bergendal et al. (2011)

Out-of-frame mutation
Nonsense c.175C > T p.R59X Yes 35a 4 Tallon-Walton et al. (2007)
Nonsense c.340A > T p.K114X Yes 32a 3 Nieminen et al. (2001)
Nonsense c.433C > T p.Q145X No 38a 5 Hansen et al. (2007)
Nonsense c.480C > G p.Y160X No 20 1 Zhu et al. (2012)
Frameshift c.59del C p.P20fsX65 Yes 31a 2 Mostowska et al. (2013a)
Frameshift c.175_183delGATACAAins288bp p.A59fsX119 Yes 19 2 Das et al. (2003)
Frameshift c.218_219insG p.G73fsX243 Yes 122 12 Stockton et al. (2000)
Zhu et al. (2012)
Frameshift c.230_242del13bp p.R77fsX4 Yes 13 1 Bergendal et al. (2011)
Frameshift c.321_322insG p.G108fsX209 Yes 44 4 Suda et al. (2011)
Frameshift c.353_354insTGCC p.S119fsX199 Yes 9 1 Mostowska et al. (2013b)
Frameshift c.619_621delATCin-s24bp p.I207fsX5 No 70 5 Mostowska et al. (2006)
Frameshift c.792_793insC p.V265fsX25 No 78 9 Frazier-Bowers et al. (2002)
Initial c.1A > G p.0? Yes 30a 2 Klein et al. (2005)
Initial c.2T > G p.0? Yes 57 5 This study
Entire gene del – – Yes 39a 2 Das et al. (2002)

*All mutations are annotated using HGVS (Human Genome Variation Society) system.
a
Primary tooth affected.

Fig. 3. Summary of teeth missing number caused by PAX9 mutations. The dashed line divided the mutations into two subsets (Left: In-frame mutations; Right: Out-of-frame
mutations). The bars indicate the average missing number with error bars representing maximum and minimum missing number. The grey bars indicate primary tooth
affected.

in a 50 –30 direction, searching for the first AUG that initiates
translation. In addition, the sequences surrounding AUG are also
important for efficient initiation to proceed. The sequence near the
first initiation codon in the PAX9 (GGAGCAaugG) matches well
with the known recognition sequence with a purine at position 3
and G at position +4 (Kozak, 1991, 1999). Therefore, the first
mutated AUG may not be recognised by most of the ribosomes. The
next in-frame unmutated AUG is located at codon 188; however,
the surrounding sequence (GTGGCCaugC) does not completely
match with the known recognition sequence. Even if PAX9 could be
translated to be similar with the other in-frame or out-frame AUG,
the paired domain of PAX9 could be affected.
In conclusion, we suggest that the heterozygous c.2T > G
mutation in PAX9 causes severe or complete inhibition of PAX9
translation at one allele and acts by inactivating one protein copy,
leading to haplo-insufficiency. And this mutation caused oligo-
dontia in the Chinese family.
148 J. Liang et al. / Archives of Oral Biology 61 (2016) 144–148
Conflict of interest
The authors declare that they have no conflict of interest.
Funding
National Natural Science Foundation of China (30930099,
81120108010).
Ethical approval
Institutional Review Board of hospital and School of Stomatol-
ogy, Wuhan University. The relevant Judgement’s reference
number 54.
Acknowledgements
We are extremely grateful to all the family members for their
enthusiastic participation in this study. The assistance of doctors in
the Departments of Clinical Laboratory and Radiology is much
appreciated. This study was supported by grants from the National
Natural Science Foundation of China (81470727, 81120108010) and
China Scholarship Council.
References
Bergendal, B., Klar, J., Stecksen-Blicks, C., Norderyd, J., & Dahl, N. (2011). Isolated
oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and
PAX9 genes. American Journal of Medical Genetics Part A, 155A(7), 1616–1622.
Chi, N., & Epstein, J. A. (2002). Getting your Pax straight: Pax proteins in
development and disease. Trends in Genetics, 18(1), 41–47.
Das, P., Stockton, D. W., Bauer, C., Shaffer, L. G., D’Souza, R. N., Wright, T., et al. (2002).
Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia.
Human Genetics, 110(4), 371–376.
Das, P., Hai, M., Elcock, C., Leal, S. M., Brown, D. T., Brook, A. H., et al. (2003). Novel
missense mutations and a 288-bp exonic insertion in PAX9 in families with
autosomal dominant hypodontia. American Journal of Medical Genetics Part A,
118A(1), 35–42.
De, C., Oster, P. J., Marks, L. A., Martens, L. C., & Huysseune, A. (2009). Dental
agenesis: genetic and clinical perspectives. Journal of Oral Pathology and
Medicine, 38(1), 1–17.
van den Boogaard, M. J., Creton, M., Bronkhorst, Y., van der Hout, A., Hennekam, E.,
Lindhout, D., et al. (2012). Mutations in WNT10A are present in more than half of
isolated hypodontia cases. Journal of Medical Genetics, 49(5), 327–331.
Frazier-Bowers, S. A., Guo, D. C., Cavender, A., Xue, L., Evans, B., King, T., et al. (2002).
A novel mutation in human PAX9 causes molar oligodontia. Journal of Dental
Research, 81(2), 129–133.
Han, D., Gong, Y., Wu, H., Zhang, X., Yan, M., Wang, X., et al. (2008). Novel EDA
mutation resulting in X-linked non-syndromic hypodontia and the pattern of
EDA-associated isolated tooth agenesis. European Journal of Medical Genetics, 51
(6), 536–546.
Hansen, L., Kreiborg, S., Jarlov, H., Niebuhr, E., & Eiberg, H. (2007). A novel nonsense
mutation in PAX9 is associated with marked variability in number of missing
teeth. European Journal of Oral Sciences, 115(4), 330–333.
Jumlongras, D., Lin, J. Y., Chapra, A., Seidman, C. E., Seidman, J. G., Maas, R. L., et al.
(2004). A novel missense mutation in the paired domain of PAX9 causes non-
syndromic oligodontia. Human Genetics, 114(3), 242–249.
Kapadia, H., Frazier-Bowers, S., Ogawa, T., & D’Souza, R. N. (2006). Molecular
characterization of a novel PAX9 missense mutation causing posterior tooth
agenesis. European Journal of Human Genetics, 14(4), 403–409.
Kim, J. W., Simmer, J. P., Lin, B. P., & Hu, J. C. (2006). Novel MSX1 frameshift causes
autosomal-dominant oligodontia. Journal of Dental Research, 85(3), 267–271.
Klein, M. L., Nieminen, P., Lammi, L., Niebuhr, E., & Kreiborg, S. (2005). Novel
mutation of the initiation codon of PAX9 causes oligodontia. Journal of Dental
Research, 84(1), 43–47.
Kozak, M. (1991). An analysis of vertebrate mRNA sequences: intimations of
translational control. Journal of Cell Biology, 115(4), 887–903.
Kozak, M. (1999). Initiation of translation in prokaryotes and eukaryotes. Gene, 234
(2), 187–208.
Lammi, L., Halonen, K., Pirinen, S., Thesleff, I., Arte, S., & Nieminen, P. (2003). A
missense mutation in PAX9 in a family with distinct phenotype of oligodontia.
European Journal of Human Genetics, 11(11), 866–871.
Lammi, L., Arte, S., Somer, M., Jarvinen, H., Lahermo, P., Thesleff, I., et al. (2004).
Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal
cancer. American Journal of Human Genetics, 74(5), 1043–1050.
Liang, J., Song, G., Li, Q., & Bian, Z. (2012). Novel missense mutations in PAX9 causing
oligodontia. Archives of Oral Biology, 57(6), 784–789.
Mitsui, S. N., Yasue, A., Masuda, K., Watanabe, K., Horiuchi, S., Imoto, I., et al. (2014).
Novel PAX9 mutations cause non-syndromic tooth agenesis. Journal of Dental
Research, 93(3), 245–249.
Mostowska, A., Kobielak, A., Biedziak, B., & Trzeciak, W. H. (2003). Novel mutation in
the paired box sequence of PAX9 gene in a sporadic form of oligodontia.
European Journal of Oral Sciences, 111(3), 272–276.
Mostowska, A., Biedziak, B., & Trzeciak, W. H. (2006). A novel mutation in
PAX9 causes familial form of molar oligodontia. European Journal of Human
Genetics, 14(2), 173–179.
Mostowska, A., Zadurska, M., Rakowska, A., Lianeri, M., & Jagodzinski, P. P. (2013a).
Novel PAX9 mutation associated with syndromic tooth agenesis. European
Journal of Oral Sciences, 121(5), 403–411.
Mostowska, A., Biedziak, B., Zadurska, M., Dunin-Wilczynska, I., Lianeri, M., &
Jagodzinski, P. P. (2013b). Nucleotide variants of genes encoding components of
the Wnt signalling pathway and the risk of non-syndromic tooth agenesis.
Clinical Genetics, 84(5), 429–440.
Nieminen, P., Arte, S., Tanner, D., Paulin, L., Alaluusua, S., Thesleff, I., et al. (2001).
Identification of a nonsense mutation in the PAX9 gene in molar oligodontia.
European Journal of Human Genetics, 9(10), 743–746.
Peters, H., Neubuser, A., Kratochwil, K., & Balling, R. (1998). Pax9-deficient mice lack
pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb
abnormalities. Genes and Development, 12(17), 2735–2747.
Schalk-van der Weide, Y., Beemer, F. A., Faber, J. A., & Bosman, F. (1994).
Symptomatology of patients with oligodontia. Journal of Oral Rehabilitation, 21
(3), 247–261.
Stockton, D. W., Das, P., Goldenberg, M., D’Souza, R. N., & Patel, P. I. (2000). Mutation
of PAX9 is associated with oligodontia. Nature Genetics, 24(1), 18–19.
Suda, N., Ogawa, T., Kojima, T., Saito, C., & Moriyama, K. (2011). Non-syndromic
oligodontia with a novel mutation of PAX9. Journal of Dental Research, 90(3),
382–386.
Tallon-Walton, V., Manzanares-Cespedes, M. C., Arte, S., Carvalho-Lobato, P.,
Valdivia-Gandur, I., Garcia-Susperregui, A., et al. (2007). Identification of a novel
mutation in the PAX9 gene in a family affected by oligodontia and other dental
anomalies. European Journal of Oral Sciences, 115(6), 427–432.
Tao, R., Jin, B., Guo, S. Z., Qing, W., Feng, G. Y., Brooks, D. G., et al. (2006). A novel
missense mutation of the EDA gene in a Mongolian family with congenital
hypodontia. Journal of Human Genetics, 51(5), 498–502.
Thesleff, I. (2006). The genetic basis of tooth development and dental defects.
American Journal of Medicine Genetics Part A, 140(23), 2530–2535.
Vastardis, H., Karimbux, N., Guthua, S. W., Seidman, J. G., & Seidman, C. E. (1996). A
human MSX1 homeodomain missense mutation causes selective tooth
agenesis. Nature Genetics, 13(4), 417–421.
Vastardis, H. (2000). The genetics of human tooth agenesis: new discoveries for
understanding dental anomalies. American Journal of Orthodontics and
Dentofacial Orthopedics, 117(6), 650–656.
Wang, Y., Wu, H., Wu, J., Zhao, H., Zhang, X., Mues, G., et al. (2009). Identification and
functional analysis of two novel PAX9 mutations. Cells, Tissues, Organs, 189(1–4),
80–87.
Wang, Y., Groppe, J. C., Wu, J., Ogawa, T., Mues, G., D’Souza, R. N., et al. (2009).
Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in
human PAX9. Human Molecular Genetics, 18(15), 2863–2874.
Wang, S. K., Chan, H. C., Makovey, I., Simmer, J. P., & Hu, J. C. (2012). Novel PAX9 and
COL1A2 missense mutations causing tooth agenesis and OI/DGI without
skeletal abnormalities. Public Library Of Science, 7(12), e51533.
Zhao, J., Hu, Q., Chen, Y., Luo, S., Bao, L., & Xu, Y. (2007). A novel missense mutation in
the paired domain of human PAX9 causes oligodontia. American Journal of
Medical Genetics Part A, 143A(21), 2592–2597.
Zhong, Q., Simonis, N., Li, Q. R., Charloteaux, B., Heuze, F., Klitgord, N., et al. (2009).
Edgetic perturbation models of human inherited disorders. Molecular Systems
Biology, 5, 321.
Zhu, J., Yang, X., Zhang, C., Ge, L., & Zheng, S. (2012). A novel nonsense mutation in
PAX9 is associated with sporadic hypodontia. Mutagenesis, 27(3), 313–317.