3+4+Supplementum/2012 - Společnost pro pojivové tkáně

Jansen type 3p22-p21.1 (parathyreoid hormone
receptor gene), with missens point
mutation, Schmid type 6q21-q22 (collagen
type X alfa 1 chain), with missens or nonsense
point mutations and deletions, and
Mc kusick type 9p13 (RNA component of
mitochondrial RNA processing endoribonuclease),
with insertions and duplications
in the promotor region or missense point
mutations in the coding region.
Multiple epiphyseal dysplasia
Heterogenous group of the AD diseases
with different chromosomal location – type
l: with chromosomal location 19p13.1, the
gene COMP encodes an extracellular pentameric
calcium binding protein in developing
bone and tendon, cause the more
severe fairbank forms of MED with severe
hip involvement, there are missense point
mutations with dominant negative effect,
this is the connection to the pseudoachondroplasia.,
type 2: with location 1p33-p32.2,
this is gene for collagen type IX alfa 2 chain,
mutations include splice point mutations
with probable dominant – negative effect,
the mutations lead to shortened collagen
IX chains (truncated protein ) and result is
abnormal mature collagen IX assembly, with
relatively mild Ribbing type MED, and type
3: 20q13.3 this is mutation collagen type IX
alfa 3 chain, splice site point mutations with
probable dominant – negative effect, which
lead to shortened collagen IC chains and
relatively mild Ribbing type.
Osteogenesis imperfecta –
heterogenous group
This is mutation of collagen type I alfa
1 chain or rarely collagen type I alfa 2
chain mutation, or another non collagen
326 14 th Prague-Sydney-Lublin
mutations at atypicall forms. Chromosomal
locations are 17q21.31-q22 or 7q22.1 respectively.
Mutational spectrum include point
mutations and deletions with loss of function
(zero effect), missense mutations,
exon skipping mutations, insertions and
deletions are with dominant negative effect.
Most cases of OI are heterozygous mutations
in one of the type I collagen genes.
Osteopetrosis
Heterogenous group, according to age
of onset and severity, benign tarda form
is located to 1p21 AD inherited, but gene
is unknown, severe congenital form with
location to 11q13.4 – q13.5, T cell immune
regulator 1 with point mutations and deletions
causing abnormal splicing, frameshift
and protein truncation with loss-of-function
effect. One of two transcripts OC116
is specific for osteoclasts. and facilitate normal
osteoclasts activity. The severe form
has own heterogenity, too. Exists another
specific 3rd form – osteopetrosis with
renal tubular acidosis in late infancy or
early childhood , with chromosomal location
8q22, there is defect of carbonic anhydrase
type II with missense, splice junction
and frameshift mutations with loss
of function effect. Carbonic anhydrase II
have direct or indirect role in osteoclastic
resorbtive process (bone acidification).
Pseudoachondroplasia
With location to the 19p13.1 and causative
gene is COMP (cartilage oligomeric
matrix protein) with point mutations and
deletions, which have dominant negative
effect. The molecular pathogenesis is similar
as at the some types of MED (previous
nosologic unit).