Human GEnetics of Amelogenesis Imperfecta Flashcards
why is Enamel unique
High mineral contenet
what are Proteins used for in Enamel
Enamel formation but not for the final product
what cleaves enamel structural proteins and when
Proteinase soon after secretion into the matrix
where do Enammel Cristals grow longer
At the enamel surface
where do Enamel crystals grow thicker
At the depth
Stages of Dental Enamel formation
Secretory stage
Maturations
what happens in the Secretory stage
Ameloblasts secrete enamel matrix to fill the full enamel thickness
what happens in the Maturation stage
Degradation of enamel matrix and mineralization
what do Ameloblasts develop in the secretory stage to help with secretion of enamel matrix
trianglular shape at the distal end that remains in the enamel shrinking until it is squeezed out of existance
How does the Triangle shape at the distal end of the Ameloblast serete enamel matrix
Only at one side of the triangle
Before the Secretory phase, what happens to the Ameloblasts
The dissolve the basement membrane and form tight junctions
what happens during the maturation stage
The basemement membrane reforms and the Ameloblasts go through ruffled and smooth phases
Roll of the Ruffled Ameloblasts
Secrete proteases and acidify to remove the enamel matrix
also help with Calcium binding
Junction of Ruffled Ameloblasts
Tight distal junctions
Junction of Smooth Ameloblasts
Leaky distal Junctions
Roll of Smooth Ameloblasts
Allow the degraded proteins to diffuse and leave
what is the space between rod and interrod enamel
Sheath space
The triangular process of the Ameloblasts
Tomes Process
What are the faces of Tomes Process
Secretory and Nonsecretory faces
what are some steps ameloblasts seem to do in the maturation stage to remove acid
Stop, remove acid by having the tight junctions get leaky, and then continue
Why do Hunter Schreger bands form
Result of a section phenomenon through two enamel rod directions
How do rods travel to the surface
Rods bend, go up and over, annd then go up again
why do rods go in a curvey pattern
allows rods to pack tightly at the enamel surface where the enamel area is greater than the dej
-occlusal surface force dissipated cervically and laterally
where do rods locate due to hunter-schreger bands
Laterally and occlusally from its point of origin
how do hunger schreger bands form around the cusp
Form in circular arrangements
How does Enamel formation start location wise around the tooth
At the cusp tip then proceeds cervically
what kind of enamel foes the Hunger-schreger bands form
Gnarled enamel
Cohorts of Ameloblasts sequentially form what type of enamel rods
Gnarled enamel rods
Junctions between the Cohorts are responsible for
Striae of Retzius
Perikymata are the surface extension of what
Lines of Retzius
what is the Neonatal line
An enlarged line of Retzius due to the stress of birth
Types of Ameloblasts
Pre-ameloblasts
Secretory ameloblasts
Maturation ameloblasts
Reduced ameloblasts
Proteins secreted in the secretory stage
Structural enamel proteins (amelogenin, Ameloblastin, Enamelin) Enamel Proteinase (matrix Metalloproteinase-20)
Proteins secreted in the Maturation stage
Enamel Proteinase (kallikrein-4)
what is Amelogenesis Imperfect
GRoup designation for a variety of inherited conditions displaying enamel malformations in the absence of non-dental phenotypes
Result of Hypoplastic Amelogenesis Imperfect
Thin enamel
What is the Defect in Hypoplastic Amelogenesis Imperfecta
Secretory stage defects
Result of Hypopmaturation Amelogenesis IMperfect
Soft enamel
Results of Hypocalcified Amelogenesis IMperfecta
Soft and Thin enamel
What is the defect in Hypomaturation Amelogenesis IMperfecta
Maturation stage defects
what does an Amelogenin mutation result in
AI on the X chromosome
where is Ameloblastin gene located
On chromosome 4
where is Enamelin gene located
On chromosome 4
roll of Amelogenin
regulate crystallite spacing
where does Ameloblastin accumulate
In the sheath space
Where is Enamelin found
Intact enamelin is restricted to the mineralization front
What structural enamel prtein is no Glycosylated
Amelogenin
what makes up 90% of the structural enamel proteins
Amelogenin
what are the Enamel proteinases
Matrix Metalloproteinase (MMP20) Kallikrein-4 (KLK4)
when is MAtrix Metalloproteinase released
Secretory stage
roll of MAtrix Metalloproteinase
Processes enamel proteins
when is Kallikrein-4 released
Transition/maturation stages
what does KAllikrein-4 do
Degrades enamel matrix
what kind of Disease does Amelogenin mutations lead to
X linked Hypoplastic AI
what chromosomes are the human Amelogenin genes fround on
X and Y chromosomes
what happens if the Amelogenin genes are knocked out from protein sectretion
the DEJ(ameloblasts extensions in the predentin) looks the same as the wild-type but with no detectable protein secretion
what happens to the Collegen as a resultl of the Amelx gene being knocked out
Initial ribbons that would form on collagen mineral are short, less organized and elongate slowly
apparent cystal fusions
what is the Amelx phenotype
Distrinctive vertical banding pattern on the enamel of affected heterozygous females due to random inactiviating the X chromsomes
what kind of disease does Ameloblastin (Ambn) mutation lead to
Autosomal recessive Hypoplastic AI
Phenotype of Ambn
Poorly formed Rods (prisms)
Shitty enamel
what does Enamelin (ENAM) mutation lead to
Autosomal Dominant Hypoplastic AI
what happens when Enam is eliminated
No enamel ribbons even after extensive dentin mineralization
what is the Phenotype if Heterozygous ENAM mutation
mild phenotype, with localized pitting defects and groove/shallow pits formed in paralel horizontal lines
what happens when Both ENAM allels are defective
No enamel layer
what does MAtrix Metalloproteinase-20 do
Secreted early in development of enamel to cleave strucutural proteins Amelogenin, enamelin, and ameloblastin
how much MAtrix Metalloproteinase-20 is present
Very small amounts
what do people with Enamel mutations often have
Severe carries
how does A westernblot lot when MMP-20 is removed
Will have one large protein left, but a lot of smaller bands will appears as cleaved products
what does mmp20 do the DEJ
Weak Dentin-Enamel JUnction
what does MMP20 mutation lead to
Hypoplastic/hypomaturation AI
Phenotype of MMP20 mutation
Pigmented hypopmaturation AI
normal size teeth, but enamel does not contrast well with dentin on radiographs
enamel tends to chip
presence of Strcutural enamel proteins and MMP20 in species with no teeth
No, since there is no selective pressure to maintain these genes
what happens when matuaration stage enamel proteins are mutated
AI
Proteins of MAturation stage
Kallikrein 4 (KLK4)
WD repeat protein 72 (WDR72)
Chromosome 4 open reading frame 26 (C4orf26)
Solute Carrier Family 24, member 4 (SLC24A4)
Roll of Kallikrein 4
Serine protease
Mutation in Kallikrein 4 leads to
Autosomal-recessive AI
roll of WD repeat protein 71
Intracellular protein
mutation of WD repeat protein 72 cuases
Autosomal recessive AI
roll of Chromosome 4 open reading fram 26
secreted to hlep enamel mature
roll of Solute carrier family 24, member 4
Proton pump that may rid enamel of protons
when is Kallikrein-4 expressed
During mid-late stage enamel develop when enamel has reached its full thickness and when proteins are actively removed rom the hardening matrix
roll of Kallikrein-4
degrades proteins to facilitate their removal from the enamel matrix
effect of REmoving Kallikrein-4
Enamel has normal thickness and rod and interrod org
However; enamel crystals do not grow together
what does A kallikrein-4 mutation lead
Autosomal Recessive Hypomaturation AI
phenotype of KLK4 mutation
ARAI normal sized teeth yellow brown Enamel is slightly opace Fracturing enamel
when is Family with Sequence similarity 83 member H
uniquitously expressed
what does Family with sequence Similarity 83 affect
dental enamel
what does Mutation in Family with sequence similarity 83 member H lead to
Autosomal dominant hypocalcified amelogenesis imperfecta
what is most common form of AI in the US
fam83H mutations for autosomal dominant hypocalcified amelogenesis imperfecta
FAM20A mutations lead to
Enamel hypoplasia Gingival hypertrophy Kidney calicifcations Enamel Renal syndrome Delayed eruption Pulp calcifications
FAM20A mutations lead to
Hypoplastic amelogeneis imperfecta Gingival hyperplasia kidney calcifaction intrapupal calcification delayed tooth eruption failure for tooth development
