Genetics of Tooth Disorders Part II

Proteins Associated with Mineralized Tissues Encoded on Chromosome 4

• SCPP proteins

• enamel extracellular matrix proteins

• dentin ECM proteins SIBLINGs

dentin ECM proteins SIBLINGs

• expressed in bone and dentin

• small regions of similarity between them

• AA sequence highly conserved across species

enamel extracellular matrix proteins

ameloblastin and enamelin

conserved chromosomal synteny

gene clustering is conserved from species to species

enamel extracellular matrix

95% mineral, 4% protein, 1% water

amelogenins

• encoded on X and Y chromosomes

• many isoforms due to alternative splicing of mRNA

• regulates growth of crystals in length

male and female amelogenin

males have two types; females have one type (6 bp shorter than Y allele)

enamelin

• regulates crystal elongation (promotes ribbon elongation and nucleation)

• chromosome 4

ameloblastin

• cement protein that integrates enamel and dentin at DEJ

• chromosome 4

amelogenesis imperfecta (AI)

• inherited abnormality affecting the enamel

• both primary and permanent dentition

• may be associated with syndrome

amelogenesis imperfecta type I

hypoplastic: defect in amount of enamel

amelogenesis imperfecta type II

hypomaturation: defect in removal of proteins from enamel

amelogenesis imperfecta type III

hypocalcified: defect in calcification

features of amelogenesis imperfecta type I

• rough pitted surface

• (+) calfication

• hard enamel

• defect in amount of enamel; very thin and cannot detect enamel on radiograph

genetic findings in hypoplastic AI

• enamelin mutations (chromosome 4)

• amelogenin mutations (chromosomes x & y)

features of amelogenesis imperfecta type II

• defect in mineralization of ECM from removal of proteins and water

• enamel is softer than unaffected enamel but stronger than hypocalcified AI

• mottled enamel w/ brown pigment

• snow-capped on incisal/occlusal surface

genetic findings in hypomaturation AI

enamelysin (MMP20) and kallikrein-4

enamelysin (MMP20)

• early protease

• secretory stage

• chromosome 11

kallikrein-4

• late protease

• transition-maturation

• chromosome 19

features of amelogenesis imperfecta type III

• matrix formation normal thickness

• no calcification

• soft enamel

• brown due to extrinsic stains

• not prone to caries

• gene FAM83H identified

  • first gene involved in AI that does not encode a secreted protein

  • associated w/ secretory vesicles

treatment of AI

• must first identify problem

• observe and describe clinical findings

• note: are both primary and perm. dentitions affected?

• ask “does this run in your family?”

• identify which type of AI it is

• risk of their children also having AI

treatment of AI

• stainless steel crowns on primary dentition

• complete coverage as early as possible on perm. dent.

• composite veneers

• bonded porcelain crowns

dentin extracellular matrix

• collagen type 1, 3, 5, 6

• hydroxyapatite > 67%

• non-collagenous proteins

  • dentin sialoprotein: DSP

  • dentin phosphoprotein: DPP

  • dentin glycoprotein: DGP

  • bone sialoprotein: BSP

  • osteopontin: OSP

  • osteocalcin: OCN

  • osteonectin: OSN

  • matrix extracellular phosphoglycoprotein: MEPE

dentinsialophosphoprotein (DSPP) gene structure

post-translational cleavage of protein: DSP, DGP, DPP

dentinogenesis imperfecta (DGI)

• inherited abnormality affecting dentin; both primary and permanent dentition

• autosomal dominant

• 1:8000 affected

• teeth appear blue-grey or amber-brown and opalescent

• roots may be narrow w/ little to no pulp chamber depending on the type of DGI

• bulbous crowns

• pulp of primary teeth may be enlarged termed “shell teeth”

• enamel splits readily from dentin when subjected to force

3 types of DGI

• type I osteogenesis imperfecta: (+) bone defects

• type II opalescent: (-) bone defects

• type III brandywine isolate: (-) bone defects

dentinogenesis imperfecta type I

• associated w/ osteogenesis imperfecta

• mutation in type I collagen

  • brittle bones

  • blue sclera

  • bitemporal bossing

  • bowing of the limbs

clinical oral manifestations DGI type I

• enamel splits away from dentin

• amber translucent color is common

• severe attrition

radiographic findings DGI type I

• obliteration of pulp chamber i.e. filled w/ reparative dentin

• small underdeveloped roots

• roots + fractures

mutations in DSPP

• dentinogenesis imperfecta types II and III

• dentin dysplasia types I and II

dentinogenesis imperfecta type II

• hereditary opalescent dentin

• not associated w/ osteogenesis imperfecta

• single mutation in DSPP gene (affects DSP region)

• first nucleotide in Exon 3 G —> T

  • may interfere w/ secretion of protein

  • may affect processing of mRNA

dentinogenesis imperfecta type III

• also called brandywine isolate

• mutation in DSPP gene shortening the protein by 6 aa

• bell-shaped crowns

• “shell teeth” more common in primary teeth

  • enlarged pulps and pulpal exposures

dentin dysplasia type I

• autosomal dominant mutations in DSPP gene

• rootless teeth

• sharp, conical-shaped roots

• both primary and permanent dentitions

• obliterated pulp chambers

• frequent abscesses

• periapical radiolucencies

• clinically may appear normal

• extreme mobility and tooth loss

dentin dysplasia type II

• coronal type

• only primary teeth are affected

• roots are present

• obliterated pulp chambers in primary teeth

• may looks similar to DGI II w/ amber transculent/opalescent color and severe attrition

• clinically, permanent teeth appear normal

• “thistle tube” shaped pulp chambers in permanent teeth

primary job of clinician

• diagnose

  • genetic disorder or pathology?

  • does this run in your family?

  • are both dentitions affected?

• educate patient on disease and potential to transfer to offspring

• proper treatment planning essential

  • coordinate w/ orthodontist, prosthodontist, geneticist, and patient’s wallet