How Mutations Affect Health and Tooth Development

Question 1

A mutation in the Type I collagen would most likely result in which of the following diseases?

Amelogenesis imperfecta
Dentinogenesis imperfecta type II
Dentinogenesis imperfecta type III
Dentinogenesis imperfecta type I

Answer 1

Dentinogenesis imperfecta type I

Question 2

Can mutations in somatic tissue be inherited?

Answer 2

no, but they can give rise to diseases such as cancer

Question 3

Can mutations in gametes be inherited?

Answer 3

yes, they will be passed onto offspring

Question 4

How many genetic mutations have been studied?

Answer 4

around 400,000
-always increasing

Question 5

What are loss of function mutations?

Answer 5

absence results in dysfunction
-mutations result in less or no function of certain proteins
-many autosomal recessive cases in enzyme deficiency

Question 6

What does it mean if something is haploinsufficiency?

Answer 6

reduced gene dosage in not sufficient to permit the cell to function properly

Question 7

What does it mean if something is dominant negative?

Answer 7

-mutation whose gene product adversely affects the normal, wild type gene product within the same cell
-usually more dangerous than mutations that cause the creation of no product at all

Question 8

what is an example of a haploinsufficiency disorder?

Answer 8

Marfan syndrome

Question 9

What is an example of a dominant negative disorder?

Answer 9

osteogenesis imperfecta

Question 10

What are the types of loss of function mutations?

Answer 10

haploinsufficiency and dominant negative

Question 11

What are gain of function mutations?

Answer 11

increased function results in dysfunction
-mutations in certain genes gain a new and abnormal function of the protein

Question 12

How many genes have been found to be associated with tooth patterning?

Answer 12

over 300

Question 13

On a pedigree, what is an unaffected male?

Answer 13

empty square

Question 14

On a pedigree, what is an affected male?

Answer 14

filled in square

Question 15

On a pedigree, what is an unaffected female?

Answer 15

empty circle

Question 16

On a pedigree, what is an affected female?

Answer 16

filled in circle

Question 17

On a pedigree, what does a single line between people mean?

Answer 17

mating

Question 18

On a pedigree, what does a double line between people mean?

Answer 18

consanguineous mating

Question 19

Where does consanguinity occur most commonly?

Answer 19

Middle East, West Asia, and North Africa

Question 20

Do issues in tooth development usually occur by themselves?

Answer 20

no, there is usually an underlying disease/disorder that is causing the abnormal tooth development
-so it is crucial as dentist to recognize the signs in the oral cavity of children

Question 21

What are the six major categories of genetic disease that affect the dentition?

Answer 21

-malocclusion
-craniofacial
-bone mass traits
-tooth agenesis
-tooth movement
-tooth development

Question 22

What does dentinogenesis imperfecta impact?

Answer 22

dentin

Question 23

What does amelogenesis imperfecta affect?

Answer 23

enamel

Question 24

What are some symptoms of ectodermal dysplasia?

Answer 24

-abnormal nails
-abnormal or missing teeth
-absent or very thin hair
-absent tears
-many other

Question 25

What syndromic associated diseases have supernumerary teeth?

Answer 25

-cleidocranial dysplasia -gardner's syndrome -trichorhino phalangic syndrome -cleft lip and palate

Question 26

are supernumerary teeth syndromic or non-syndromic?

Answer 26

both

Question 27

Characteristics of cleidocranial dysplasia:

Answer 27

-mutation in RUNX2 gene -delayed closure of sutures, aplastic or hypoplastic clavicle formation, short stature, and dental abnormalities

Question 28

What does RUNX2 do?

Answer 28

master regulator of osteoblastogenesis and bone formation

Question 29

What is hypodontia?

Answer 29

missing one to five teeth

Question 30

What is oligodontia?

Answer 30

missing six or more teeth

Question 31

What is andodontia?

Answer 31

missing all teeth -most severe and rare form (mostly syndromic)

Question 32

Worldwide prevalence of hypodontia:

Answer 32

6.4%

Question 33

Worldwide prevalence of missing third molars:

Answer 33

22.6%

Question 34

Worldwide prevalence of missing primary teeth:

Answer 34

rare 0.1-2.4%

Question 35

How many syndromes are associated with tooth agenesis?

Answer 35

over 60 different conditions

Question 36

what is the most common presentation of tooth agenesis?

Answer 36

isolated, non-syndromic trait

Question 37

Percentage of missing mandibular 2nd premolar not associated with a syndrome:

Answer 37

3%

Question 38

Percentage of missing maxillary lateral incisor not associated with a syndrome:

Answer 38

1.7%

Question 39

Percentage of missing maxillary 2nd premolar not associated with a syndrome:

Answer 39

1.5%

Question 40

Percentage of missing mandibular central incisor not associated with a syndrome:

Answer 40

0.3%

Question 41

Two most common mutated genes associated with tooth agenesis:

Answer 41

MSX1 and PAX9

Question 42

what does a mutation in AXIN2 cause?

Answer 42

tooth agenesis and colorectal cancer

Question 43

what are the major proteins of enamel?

Answer 43

-amelogenin -ameloblastin -enamelin -Kallikrin 4 -Mmp-20

Question 44

What does amelogenin do?

Answer 44

stabilize the amorphous Ca-P phase -self assemble and form HAP structure *important in forming enamel

Question 45

What does ameloblastin do?

Answer 45

is it a cell adhesion protein, controls cell differentiation, maintain rod integrity

Question 46

What does enamelin do?

Answer 46

cooperates with amelogenin to control mineral nucleation and elongated growth

Question 47

What does Kallikrin 4 do?

Answer 47

digest enamel proteins during maturation stage helping their removal and hardening the final layer of enamel

Question 48

What does Mmp-20 do?

Answer 48

cleave amelogenin, ameloblastin, and enamelin at the secretory phase to make stable intermediates with defined functions

Question 49

What does amelogenesis imperfecta cause?

Answer 49

unusually small, discolored, pitted or grooved, and prone to rapid wear and breakage *no enamel

Question 50

what is the major component of dentin?

Answer 50

type I collagen

Question 51

what are the dentin ECM molecules?

Answer 51

Type I collagen & SIBLING proteins SIBLING proteins: -dentin sialophosphoproteins (DSPP) -dentin matrix protein 1 (DMP1) -bone sialoprotein -osteopontin -MEPE

Question 52

What does dentin sialophosphoproteins do?

Answer 52

immediately cleaved after secretion into DSP, DGP and DPP

Question 53

What does dentin matrix protein 1 do?

Answer 53

made by odontoblasts and early stage osteocytes

Question 54

What does bone sialoprotein do?

Answer 54

play a role in biomineralization

Question 55

What does osteopontin do?

Answer 55

HA binding and contain an RGD motif -is a mineralization inhibitor

Question 56

What is MEPE?

Answer 56

matrix extracellular phosphoglycoprotein -contains an RDG motif and in bone appear to be an inhibitor of bone mineralization

Question 57

What is dentinogenesis imperfecta?

Answer 57

disorder of tooth development that causes teeth to be discolored and translucent -teeth are also weaker than normal

Question 58

What is type I dentinogenesis imperfecta?

Answer 58

associated with osteogenesis imperfecta -bone and teeth are both easily broken -primary teeth more affected than permanent

Question 59

What is type II dentinogenesis imperfecta?

Answer 59

occur in those without any other inherited disorders -affects the baby teeth more

Question 60

What is type III dentinogenesis imperfecta?

Answer 60

occur in those without any other inherited disorders -affects both dentitions equally -dentin is extremely thin and the pulp chambers are enlarged teeth are referred to as "shell teeth"

Question 61

mutations in COL1A1 or COL1A2 cause what?

Answer 61

osteogenesis imperfecta -dentinogenesis imperfecta type I occurs as part of OI

Question 62

What has a deficiency in dentin sialophosphoprotein (DSPP) been associated with?

Answer 62

dentinogenesis imperfecta II and III

Question 63

what is dental dysplasis?

Answer 63

milder dentin defects than DI-II&III *mutation in a signal peptide (Y6D) of DSPP causing reduced amount of DSPP secreted into dentin matrix

Question 64

What are the most common type of genetic disorders?

Answer 64

genetic diseases of the craniofacial skeleton and dentition

Question 65

What protein is associated with dentinogenesis imperfecta?

Answer 65

type I collagen