3+ 4/2002 - Společnost pro pojivové tkáně

hemidysplasia with ichtchyosiform erythroderma
and limb defects, a rare inborn disorder
which affects bone and skin in females
and is presumably lethal in males. NSHDL is
involved in C4 sterol demethylation but its
precise biochemical function remains to be
clarified. Nonsense and missense mutations
in the same gene underly the Bare patches
and Striated mutations in mice. Recurrent
missense and nonsense mutations in
Emopamil binding protein on Xp11.22 are
found in patients with X chromosomal dominant
chondrodysplasia punctata. CDPX2 is
characterized by skeletal (epiphyseal stippling,
limb shortening, short stature) and
epidermal (atrophy, ichtchyosis, hyperkeratosis)
manifestations as well as occasional
sectorial cataracts. The mouse mutant Tattered
carries a missense mutation in EBP.The
clinical differentiation between CHILD syndrome
and CDPX 2 is controversial. The
morphological phenotypes of Bare patches
and Tattered are similar to each other and
ressemble CHILD syndrome as well as
CDPX2 including lethality in male embryos.
Cholesterol crossfeeding between cell
patches in which either the X chromosome
carrying the wildtype or the mutant allele
are active possibly explains why neither in
CHILD syndrome nor in CDPX2 total cholesterol
levels are reduced. In contrast substantially
reduced total sterol concentrations
are a hallmark of the more frequent autosomal
recessive Smith-Lemli-Opitz RSH syndrome
(SLOS MIM 270 400) due to mutations
in DHCR7 in 11q13.
SLOS is characterized by dysmorphogenesis
(e.g. syndactyly, heart and lung
defects), failure to thrive and mental retardation
or autism. A recently described
induced mouse mutant in DHCR 7 had the
biochemical characteristics of the SLOS and
most surprisingly symptoms of severe neu-
rological deficits such as reduced physical
activity and uncoordinated swallowing.
THROMBOCYTOPAENIA – ABSENT
RADIUS SYNDROME (TAR)
A CLINICAL GENETIC STUDY
K. L. Greenhalgh et al., Bristol, London, Geneva
Information regarding the phenotype of
TAR syndrome is largely based on single
case reports. In order to delineate the phenotype,
32 patients diagnosed with TAR
syndrome underwent clinical and cytogenetic
analysis. All cases except 1 had bilateral
radial dysplasia. The thumbs were present
in all cases but morphology and
function were abnormal. Lower limb
defects occured in 47 % cardiac anomalies
(e.g. tetralogy of Fallot) in 16 %. Thrombocytopaenia
may be as asymptomatic and
remain undetected until later life. Early
detection is associated with low morbidity,
highlighting the value of haematological
investigation in patients with radial aplasia.
Previous reports of urogenital abnormalities
were rare, however in this study anomalies
were found in 25 %. of cases.The association
of TAR syndrome and cows milk
intolerance is well described, in this study
43 % of cases showed cows milk intolerance
and 25 % had experienced prolonged
bouts of gastroenteritis. Three atypical
cases were found. Two showed features of
Roberts syndrome and the third have mental
retardation and genitourinary abnormalities
suggestive of DK phocomelia. Four sib
pairs were found. A female excess (23
female, 8 male, one case unknown) was
observed. Chromosome breakage studies
were normal in all cases tested.Two further
cytogenetic abnormalities are under investigation
and have provided useful candidate
genes for further study based on role in
POHYBOVÉ ÚSTROJÍ, ročník 9, 2002, č. 3+4 129