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In researching this PBL I found it necessary to have a basic understanding of the structure of both primary and permanent teeth, therefore, I will start by introducing this topic. I will then go into detail about normal enamel formation and explain the condition Amelogenisis Imperfecta. Lastly, I will display an understanding of what genes are and the different inheritance patterns that can be seen; relating to Amelogenisis Imperfecta.
Structure of primary and permanent teeth
All human teeth have a crown (the visible part) and a root (the part hidden under the gum). Teeth vary in shapes and sizes depending on the function but all have the same principal layers. In the centre of the tooth is pulp tissue encased in the pulp cavity which has a very good blood and nerve supply. The layer surrounding the pulp is dentine, which composes the majority of the tooth and spans the whole length; it is a hard tissue but is porous and is therefore not strong enough to withstand the constant abrasion. For this reason, the dentine of the crown is covered with enamel; a very hard mineral surface and the root of the tooth is embedded in cementum; another mineral surface. The root is then held in place by periodontal ligaments attached to the surrounding bone .
Cross-section of a tooth
This image displays the layers I have described above .
Primary teeth develop during pregnancy and erupt during infancy. They are made up of incisors, canines and molars. The crown is to aid the chewing and tearing (depending on which tooth) of food and the root is there to anchor the tooth in place and provide a pathway for blood vessels. The layer of enamel on primary teeth is 0.5-1mm thick .
Permanent teeth develop from birth to 7 years old, grow up from the root of primary teeth and replace them during childhood. They are made up of incisors, canines, premolars and molars. The functions are the same except the root of the tooth has an additional function of supplying the pulp with nerves. The layer of enamel on permanent teeth on contrast is 1-2mm thick .
Normal formation of enamel
Enamel is composed of tightly packed hydroxylapatite crystals, arranged into rods, with small amounts of organic material and water in between . The formation of enamel is directed by specialised cells called ameloblasts. There are a total of five stages in the life cycle of an ameloblast that are of significance.
Life cycle of an Ameloblast
Cells of the inner enamel surface, which are derived from ectoderm, multiply to form the shape of the tooth (with its cusps and indentations). At the end of this stage they stop multiplying and begin to terminally differentiate into ameloblasts .
Cells of inner enamel surface differentiate into 'preameloblasts' by reorienting their organelles and elongating the cell body. The cells also have a secretory side to them, which is orientated towards the dentine of the tooth to allow migration of ameloblasts as they deposit proteins onto the tooth .
After the formation and mineralisation of dentine has occurred, preameloblasts differentiate into 'secretory ameloblasts' and start to synthesis and secrete enamel matrix (comprised of proteins amelogenin, enamelin and ameloblastin), which begins more at the cusps of the teeth and continues down to the cervix of the crown .
Once secretion of enamel matrix is completed, the secretory ameloblast differentiates again into a 'maturation ameloblast'. There are two forms of maturation ameloblast that control the mineralisation of enamel, which begins as soon as enamel matrix is laid down. Ruffle-ended ameloblasts allow mineralisation by transporting the essential minerals (calcium, phosphate and smaller amounts of fluoride)  to the matrix and the smooth-ended ameloblasts resorb much of the water and proteins from the enamel matrix .
On the completion of enamel formation, the ameloblasts then 'de-differentiate' and form the reduced enamel epithelium, which plays an important role in the eruption of teeth .
Amelogenesis imperfecta, is an inheritable disorder where the enamel of the tooth is either hypomineralised (has a deficiency of mineral incorporated into it) or hypoplastic (deficiency in the amount of enamel matrix secreted, hence acquiring only a thin layer of enamel) due to disturbances to the secretion or maturation of the enamel matrix. Amelogenesis Imperfecta affects both the structure and appearance of enamel on both primary and permanent teeth, resulting in sensitive teeth that are discoloured, may have pits and grooves, be unusually small in size and be susceptible to breakage .
Types of Amelogenesis Imperfecta are categorised into 'hypoplastic', 'dysmineralised' and 'hypomineralised' based on their appearance.
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A, B, C and D are hypoplastic forms of Amelogenesis Imperfecta.
E and F are dysmineralised forms in which the enamel is rough, soft and discoloured.
G and H are hypomineralised forms, which can be mistaken for fluorosis as white specs are present, in which the enamel is normal in thickness and hardness otherwise .
These categories can be subdivided further based on the inheritance pattern. The disorder can be inherited in three ways; autosomal dominant or recessive, and X-linked recessive .
DNA and the Genetic Code
DNA is stored in a cell as 22 pairs of autosomal chromosomes and a pair of sex chromosomes. During fusion of sex cells, which contain 22 single autosomal chromosomes and a single sex chromosome (either X or Y), DNA is combined; causing variation from person to person. Males have XY sex chromosomes and females have XX sex chromosomes. DNA is composed of monomers called nucleotides which can then be broken down further into deoxyribonucleic acid, phosphate and a base (adenosine, guanine, cytosine or thymine). Monomers bond together to form polymers and in DNA, there are two polymer chains which form a double helix shape by complementary base pairing  as can be demonstrated from the diagram below.
On a larger scale, sections of the double helix shape can be grouped together to form genes. Each gene is made up of introns (coding section) and exons (non-coding section that is spliced during transcription) which contain the information needed to synthesis a specific protein or other cell component necessary for life .
During translation of a gene into a protein, it is the sequence of bases in a gene that are read .
The genetic code refers to the universal rule that a codon codes for a specific amino acid so that when a sequence of codons are read, a chain of amino acids (which forms a protein) is built up. There can be different combinations of bases in a codon, for example, TAG= thymine, adenosine followed by guanine which allows for different codes to code for different amino acids. However, there are a total combination of 64 different codons and only 20 amino acids, therefore there is more than one code for each amino acid, three codons (stop codons) do not code for any amino acids and represent the end of an amino acid chain, and there is only one particular codon that can start the synthesis of an amino acid chain .
This table demonstrates the sequence of three bases that make up each codon, which codes for a specific amino acid .http://biology.kenyon.edu/courses/biol114/Chap05/code.gif
DNA is a very complex molecule and any error in the sequence of nucleotide bases is called a mutation. Mutations are mostly a random process, with a slightly higher risk of occurring in certain DNA sequences. There are two types of cells that can be affected; germ cells (sex cells that go on to produce gametes) and somatic cells (cells in other tissues). When a mutation arises in a germ cell, the mutation is then inherited to the next generation where as when a mutation arises in a somatic cell, the mutation is only passed on to cells derived from the original problematic cell.
Most mutations that arise are 'neutral mutations', which have no effect on the person. This occurs when a mutation arises within introns as these sections are not used to create the protein, and also when the mutation does not change the amino acid being coded for, which is possible as there is more than one code for most amino acids.
Most mutations that are not neutral are harmful, but fortunately most are also recessive, which means the mutation is only expressed if both of the genes are mutant and normal cell functioning resumes if only one is mutant .
Examples of harmful mutations include; 'missense mutation' when the alteration of a DNA base pair causes a substitution of an amino acid for a different one, 'nonsense mutation' when the substitution of an amino acid stops the building of the protein completely, 'insertion' when an extra piece of DNA is added and 'deletion' when a piece of DNA is removed . As proteins have very specific bonding and shapes, any one of these mutations can result in a different functioning or no functioning of the protein at all.
Genes can be referred to as 'dominant' or 'recessive', depending on how they are expressed within a pair. If one gene is expressed and one isn't, then they are said to be dominant and recessive respectively. However, if two dominant or two recessive genes are inherited, both genes from that pair will be expressed equally.
Autosomal dominant inheritance refers to the inheritance of a dominant faulty gene, which will be expressed in the individual and cause subsequent issues. The correct functioning gene is recessive and hence, not expressed in the presence of a dominant form. This form of inheritance is only possible if the parent shows signs of the mutant gene.
Autosomal recessive inheritance refers to the inheritance of two faulty recessive genes, one from each parent, which causes varying problems, dependant on which gene is affected. It is possible to have autosomal recessive inheritance of a medical condition even if both parents show no signs, providing both parents are carriers of the recessive gene and it is passed on in both gametes.
X-linked recessive inheritance refers to the inheritance of one or two (depending on the sex of the person) recessive genes from the X sex-cell chromosome. In the case of X-linked recessive inheritance, a female requires both X chromosomes to be affected for the gene to be expressed. However, as a male only has one X chromosome, only the mother is required to pass the recessive gene on. This type of inheritance is more common among males.
This diagram illustrates X-linked recessive inheritance where neither parents show symptoms but the Son does .http://www.retinaaustralia.com.au/images/X-linkedRecessive.gif
Genes associated with Amelogenesis Imperfecta
Enamel formation is controlled by genes in the way that the proteins required can only be produced if the gene for that protein is present. Any defects in the genes can cause malformed enamel without affecting other parts of the body, depending on which gene is affected .
PERP is a protein, coded for by the PERP gene, which regulates enamel formation by controlling gene expression and allowing the ameloblasts to adhere to the adjacent layer (stratum intermedium) of the tooth. A lack of it is shown to down regulate the expression of genes necessary for enamel formation .
AMEL is a gene which codes for the protein amelogenin, essential for normal enamel development. AMELX is located on the X sex chromosome and is responsible for the majority of the bodys supply while AMELY is located on the Y sex chromosome and produces a lot less. Mutations to AMELX gene, depending on how severe the change, has been shown to interfere with the organisation of crystals within enamel or prevent the production of amelogenin at all .
ENAM is a gene which codes for the protein enamelin, described above to have a crucial role in the formation of enamel. Mutations in this gene have been found in patients with both autosomal dominant and autosomal recessive forms of Amelogenesis Imperfecta. In autosomal dominant forms, the enamelin produced is either severely reduced in amount or a shorter, inadequate version is produced instead. The resulting enamel is very thin or absent .
AMBN is a gene which codes for the protein ameloblastin, important for the formation of enamel matrix. Mutations of this gene, inherited in an autosomal dominant pattern, have been associated with Amelogenesis Imperfecta .
MMP20 codes for a protein, enamelysin, which breaks the proteins in enamel matrix into smaller pieces, allowing for them to be resorbed from enamel, and hence become harder. In autosomal recessive Amelogenesis Imperfecta, mutations have been found in this gene which halts the production of enamelysin .
In conclusion, the development of Amelogenesis Imperfecta is hereditary and due to mutations in various genes. Currently, there is no way of preventing this development and so the resulting softer, more sensitive teeth often need protection using crowns or composite restoration .