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

neural tube defects
Are polygenic, with chromosomal location
1p36.3 for gene MTHFR, with polymorphic
missense point mutations 4q12
for gene platelet derived growth factor alfa
receptor with polymorphic promotor haplotypes
and 20p11.2 with PAX 1 gene with
missense point mutation.
Median cleft palate
etiologically similar as previous, it is
one part of midline defects. the m,ajority
of CP are regarded as non syndromic and
we propose the same mutations spectrum
as the previous nosologc unit.
Cleft lip and palate (ClP)
CLP occuring alone is etiologically distinct
from syndromologic CLP. The majority
of CLP are regarded as non syndromic,
where the clefts occur without other
anomalies. The remaining syndromic cases
have additional characteristic features
that can be subdivided into categories of
chromosomal abnormalities, recognizable
Mendelian single gene syndromes, teratogenic
effects and various unknown syndromes.
Craniofacial development is highly
complex with a large array of genes implicated.
Combined with multigeniic inheritance
and the influence of non-genetic factors,
identifying the key genes in human
CLP represents a major challenge, In addition
to the direct analysis of functional
candidates, much effort hase gone into
linkage and/or candidate gene directed
association studies. A major drawback lies
in the analysis of patients with heterogeneous
etiology, since this dilutes the chances
of finding positive gene-phenotype cor-
328 14 th Prague-Sydney-Lublin
relations. To date four genome-wide scans
for CLP have been published, one using
sib pair analysis in an English population,
one using multiplex families of Chinese
origin, one using multiplex families from
North and South America and the other
using two large Syrian families. The four
studies do not generally concur on significant
or highly suggestive regions, probably
reflecting the diverse populations investigated.
An exceptiuon to this a region on
2q, which overlaps between the Chinese
study and a subset of the American families.
A numebr of new genome scans have
been presented at the American Society of
Human Genetics 2003 meeting, including
a meta-analysis totaling 11 studies. Some
regions consistent with previous linkage
or candidate gene association studie have
been highlighted such as 2p13 (TGFA),
Osteoarthrosis
Heterogenic group, with chromosomal
location 2q12 – q13 (?), 11q13.2 – q13.3
(gene ?) and 12q13.11-q13.2 for col2alfa 1.
Osteoporosis
Heterogenic group, 7 chromosomal
location with 4 knowing genes and with
polymorphic mutational spectrum.
key words: bone, cartilage, tendons
and teeth – causative genes – molecular
pathogenesis – mutational spectrum and
correlation to the phenotype