POST GRADUATE STUDENT
DEPARTMENT OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS
GOVT.DENTALCOLLEGE AND RESEARCH INSTITUTE, BANGALORE.
2. / NAME OF THE INSTITUTE / GOVERNMENTDENTALCOLLEGE AND RESEARCH INSTITUTE, BANGALORE.
3. / COURSE OF STUDY AND SUBJECT / MASTER OF DENTAL SURGERY IN ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS.
4. / DATE OF ADMISSION TO COURSE / 01.06.2010
5. / TITLE OF THE TOPIC:
“A COMPARISION OF SKELETAL AND DENTAL PATTERNS IN PATIENTS WITH MULTIPLE CONGENITAL MISSING TEETH AND EVALUATING THE SIGNIFICANCE OF PAX9 GENE IN OLIGODONTIA-A CLINICAL AND GENETIC PROSPECTIVE STUDY. ”
6. / BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY: -
Agenesis of tooth is most common dental anomaly occurring in up to 20% of population.1 Agenesis of one or more teeth is called ‘hypodontia’ and agenesis of more than 6 teeth, excluding third molars is called ‘oligodontia’ or ‘severe hypohontia’.Pax9 gene, which belongs to pax gene family, is expressed in pharyngeal pouches, developing vertebral column and neural crest derived mesenchyme of maxillary and mandibular arches, contributing to palate and tooth formation.2 A novel missense mutations gly6arg[G6R] and ser43lys[S43K] in paired domain of pax9 shown to be associated with varying degrees of tooth agenesis.3 Dental consequences include malocclusion due to improper position of teeth, deficient growth of alveolar process, excessive space in dental arches and extreme upright position of maxillary incisors.4,5 skeletally, chin angle is reduced when mandibular anterior teeth are missing, retrognathism of both maxillary and mandibular arches seen reflecting reduced size of both jaws.4,5 It is also demonstrated that teeth located near the ends of peripheral nerve branches are most often affected by agenesis and are associated with absence of mandibular canal.6
Hence the aim of this study is to compare skeletal and dental patterns in patients with congenital absence of teeth and evaluating the significance of S43K position of pax9 in multiple congenital missing teeth in multiethnic south Indian population.
7.
/ 6.2 REVIEW OF LITERATURE
1. Direct sequencing of exon 2 to4 of pax9 revealed that a cytosine insertion mutation at nucleotide 793, leading to premature termination of translation of amino acid 315, this conclude that oligodontia is due to allelic heterogeneity in pax9.1
2. All mutations of pax9 associated with selective tooth agenesis were only found in heterozygosis, suggesting that mutant phenotypes were caused by haploinsuffiency and reinforcing the pivotal importance of this gene in tooth development.2
3. Direct sequencing analysis revealed two different mutation in exon2 of pax9.The two related individuals[familial cases] carried a double nucleotide mutation, G128A and C129A, which results in substitution of serine by lysine in amino acid 43[S43k]. Individuals with S43K mutations consisted of peg shaped lateral incisors and missing molars, premolars and canines. In sporadic cases a novel heterozygous missense mutation G16A had caused a change from glycine to arginine at amino acid 6[G6R]. Individuals with G6R mutations had missing mandibular incisors and maxillary premolars.3
4. It is demonstrated that teeth located near the ends of peripheral nerve branches are most often affected by agenesis and are associated with absence of mandibular canal.4
5. Hand tracing of lateral cephalograph of individuals having multiple congenital missing teeth with following landmarks- sella turcica(s), nasion(n), porion(po), orbitale(or), basion(ba), ANS, A-point, upper incisor apex(UIA), upper incisor edge(UIE), lower incisor edge(LIE), infra dentale(id), B-point, menton(me), soft tissue glabella(SGLB), sub nasale(sn), and soft tissue pogonion(pog’) reveals that intermaxillary relationships in congenital missing teeth group had bimaxillary retrognathism. In vertical dimensions, the Frankfort-mandibular plane angle and lower facial height to total facial height ratio were similar to classic norms, with a larger range and skewed towards lower values.
6.3 OBJECTIVE OF STUDY:-
- To compare skeletal and dental patterns in patients with congenital absence of teeth.
- To evaluate the significance of S43K position(Single nucleotide polymorphism) of pax9 in patients with multiple congenital missing teeth
30 randomly selected individuals showing non-syndromic multiple congenital missing teeth and 30 normal subjects with all the teeth present above age of 18 years, will be recruited from Department of Orthodontics and Dentofacial Orthopedics, Government Dental College and Research Institute, Bangalore. Consent will be obtained from all participants including patients and their parents/guardians.Impression of both maxillary and mandibular arches will be made to obtain study models of all participants. All the patients and participants will be subjected to radiographic examination to get their intra oral periapical radiograph (IOPA), orthopentamograph (OPG) and lateral cephalograph.
Out of these 30 affected clinical cases, only those patients having vast deviation from the normal clinical values will be subjected for S43K mutation analysis of pax9 to explore the genetic effect on clinical parameters. A salivary sample will be collected,Genomic DNA will be isolated by DNA extraction kit and amplified by polymerase chain reaction (PCR). Further genetic evaluation will be done to check the status of S43K (amino acid) position of pax9. As quantitative clinical parameters are used, a student t-test will be used for statistical analysis.
7.2 Does the study require any investigations or interventions to be conducted
on patients or other humans or animals?
YES
7.3 Has ethical clearance been obtained from your institution in case of 7.2?
WILL BE OBTAINED
8.
/ LIST OF REFERENCES:
1.Frazier-Bowers SA, Guo DC, Cavender A, Xue L, Evans B, King T, Milewicz D, D'Souza RN.A Novel Mutation In Human PAX9 Causes Molar Oligodontia.J Dent Res. 2002 Feb;81(2):129-33.
2.Pereira TV,Salzano FM,Mostowska A,Trzeciak WH,Ruiz-Linares A,Chies JA,Saavedra C,Nagamachi C,Hurtado AM,Hill K,Castro-de-Guerra D,Silva-Júnior WA,Bortolini MC Natural Selection And Molecular Evolution In Primates PAX9 gene, A Major Determinants of Tooth Agenesis.Proc Natl Acad Sci U S A.2006 Apr 11;103(15):5676-81
3.Wang Y,Wu H,Wu J,Zhao H,Zhang X,Mues G,D'Souza RN,Feng H,Kapadia H. Identification and Functional Analysis of Two Novel PAX9 Mutation..Cells Tissues Organs.2009;189(1-4):80-7
4.Kapadia H,Frazier-Bowers S,Ogawa T,D'Souza RN. Molecular Characterization Of A Novel PAX9 Missense Mutation Causing Posterior Tooth Agenesis. . Eur J Hum Genet.2006 Apr;14(4):403-9.
5.Ben-Bassat Y, Brin I.Skeletal And Dental Patterns In Patients With Sever Congenital Absence Of Teeth.Am J Orthod Dentofacial Orthop. 2009 Mar;135(3):349-56.
6.McNamara C,Foley T,McNamara CM. Multidisplinary Management Of Hypodontia In Adolescents: Case Report.J Can Dent Assoc.2006 Oct;72(8):740-6.
9. / SIGNATURE OF THE CANDIDATE
10. / REMARKS OF THE GUIDE / This study has not been done previously in the department.
11. / NAME AND DESIGNATION OF
11.1 GUIDE
11.2 SIGNATURE / DR. RAMAKRISHNA.H.C. M.D.S
READER/ ASSISTANT PROFESSOR DEPARTMENT OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS,
GOVERNMENT DENTAL COLLEGE AND RESEARCH INSTITUTE,
BANGALORE.
11.3 CO-GUIDE
11.4 SIGNATURE / DR.V.SREENIVAS PRASAD
MDS,DNB&Ph.D(molecular genetics)
READER/ ASSISTANT PROFESSOR
DEPARTMENT OF ORAL AND MAXILLOFACIAL SURGERY.
GOVERNMENT DENTAL COLLEGE AND RESEARCH INSTITUTE,
BANGALORE.
11.5HEAD OF THE DEPARTMENT
11.6 SIGNATURE / DR. SHASHIKALAKUMARI V. M.D.S
PROFESSOR & HEAD OF DEPARTMENT
DEPARTMENT OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS,
GOVERNMENT DENTAL COLLEGE AND RESEARCH INSTITUTE,
BANGALORE.
12. / 12.1 REMARK OF THE CHAIRMAN AND PRINCIPAL
12.2 SIGNATURE
1