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amelogenesis imperfecta
Heterogenic group of genes: AMELX
(amelogenin): located at Xp22.23-p22.1,
base 11 221 453 – 11 228 801. Amelogenin
is the principial protein related to the formation
of human dental enamel. X-linked
form arise from mutation in the AMELX.
The formation is controlled in ameloblasts
through the interaction of a number
of organic matrix molecules. ENAM
(enamelin): 4q13.3, base 71 713 324 –
71 731 399. The enamelin gene, ENAM,
is implicated in the pathogenesis of the
dominant forms of AI. MMP 20 (matrix
metallopeptidasis, matrix metalloproteinasis
or enamelysin): 11q22.3 – q23, base
101 952 775 – 102 001 272. KLK 4 gene for
kalikrein is located at chromosome 19q13.3
– q13.4. AMBN gene for ameloblastin is
located at 4q21, TUFT 1 gene for tuftelin
is located to the 1q21 chromosomal area,
AMELOTIN gene is located at 4q13. DSPP
gene (for dentin sialoprotein) is located to
the 4q21.3, Note the connection between
ENAM and AMELOTIN and connection
between AMBN and DSPP.
Campomelic dysplasia
The gene SOX 9 (SRY related box 9) is
located at 17q24.3. We know point mutations
(missense, nonsense and splice) deletions
and insertions with a loss-of-functions
effect (haploinsufficiency). Some
cases are caused by spectrum chromosome
breakage due, for example, to a translocations,
which exerts a „positional“ effect.
SOX 9 encodes 509 amino acid transcription
factor containing an 80 amino acid
SOX 9 is a major regulator of both sex
determination and cartilage formation.
This unique double role account for the
324 14 th Prague-Sydney-Lublin
phenotypic findings of tracheomalacia,
campomelia and sex reversal in chromosomal
males.
dentinogenesis imperfecta
Heterogenous group, type I occurs in
people who have osteogenesis imperfecta
with similar dental abnormalities as bone
abnormalities. Dentinogenesis imperfecta
type II and III usually occur in people without
other inherited disorders. Mutations
in the DSPP gene have been identified in
people with dentinogenesis imperfecta type
II and type III. Mutations in this gene are
also responsible for dentin dysplasia type
II. Dentinogenesis type I occurs as part of
osteogenesis imperfecta, which is caused
by mutations in one of several other genes
– colalfa1 chain or col1 alfa2 chain. In the
molecular pathogenesis DSPP gene provides
instructions for making two proteins that
are essential for normal tooth development.
These proteins are involved in the formation
of dentin, which is bone-like substanceš that
makes protective middle layer of each tooth.
DSPP gene mutations alter the proteins
made from the gene, leading to the production
of abnormally soft dentin. Teeth with
defective dentin are discolored, weak, and
more likely to decay and break. It is unclear
wether DSPP gene mutations are related to
the heaering loss found in a few older individuals
with dentinogenesis imperfecta type
II. One cope of the altered gene in each cell
is sufficient to cause the disoder.
Chondrodysplasia punctata
Heterogenic group of similar diseases.
The causative genes are: RCDP 1 – PEX
7 wit location at 6q22-24 (s.c. peroxisomal
assembly gene 7), this type of disease