CONTEXT: The low bone mineral density (BMD) and alterations in bone geometry observed in patients with Turner syndrome (TS) are likely caused by hypergonadotropic hypogonadism and/or by haploinsufficiency of the SHOX gene. OBJECTIVE: Our objective was to compare BMD, bone geometry, and strength at the radius between prepubertal girls with TS and children with isolated SHOX deficiency (SHOX-D) to test the hypothesis that the TS radial bone phenotype may be caused by SHOX-D. DESIGN AND SETTING: This comparative cross-sectional study was performed between March 2008 and May 2011 in 5 large centers for pediatric endocrinology. PATIENTS: Twenty-two girls with TS (mean age 10.3 years) and 10 children with SHOX-D (mean age 10.3 years) were assessed using peripheral quantitative computed tomography of the forearm. MAIN OUTCOMES: BMD, bone geometry, and strength at 4% and 65% sites of the radius were evaluated. RESULTS: Trabecular BMD was normal in TS (mean Z-score = -0.2 ± 1.1, P = .5) as well as SHOX-D patients (mean Z-score = 0.5 ± 1.5, P = .3). At the proximal radius, we observed increased total bone area (Z-scores = 0.9 ± 1.5, P = .013, and 1.5 ± 1.4, P = .001, for TS and SHOX-D patients, respectively) and thin cortex (Z-scores = -0.7 ± 1.2, P = 0.013, and -2.0 ± 1.2, P < .001, respectively) in both groups. Bone strength index was normal in TS as well as SHOX-D patients (Z-scores = 0.3 ± 1.0, P = .2, and 0.1 ± 1.3, P = .8, respectively). CONCLUSIONS: The similar bone geometry changes of the radius in TS and SHOX-D patients support the hypothesis that loss of 1 copy of SHOX is responsible for the radial bone phenotype associated with TS.
- MeSH
- aberace pohlavních chromozomů MeSH
- dítě MeSH
- genetické asociační studie MeSH
- genetické nemoci vrozené genetika metabolismus patologie patofyziologie MeSH
- haploinsuficience * MeSH
- homeodoménové proteiny genetika metabolismus MeSH
- kosti a kostní tkáň chemie patologie MeSH
- kostní denzita MeSH
- lidé MeSH
- mechanické jevy MeSH
- mladiství MeSH
- mutace MeSH
- poruchy růstu etiologie MeSH
- protein SHOX MeSH
- průřezové studie MeSH
- radius MeSH
- Turnerův syndrom genetika metabolismus patologie patofyziologie MeSH
- vývoj dítěte MeSH
- vývoj kostí * MeSH
- vývojové onemocnění kostí etiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- homeodoménové proteiny MeSH
- protein SHOX MeSH
- SHOX protein, human MeSH Prohlížeč
Chromatin structure and its changes or maintenance throughout developmental checkpoints play indispensable role in organismal homeostasis. Chromatin remodeling factors of the SWI/SNF2 superfamily use ATP hydrolysis to change DNA-protein contacts, and their loss-of-function or inappropriate increase leads to distinct human pathologic states. In this review, we focus on the translational view of human pathologic physiology involving SWI/SNF2 superfamily, combining latest finding from basic and clinical research. We discuss in mechanistic terms the consequences resulting from dose alteration of the SWI/SNF2 superfamily ATPases and emphasize the necessity of future human subject-based studies.
- MeSH
- chromatin metabolismus MeSH
- chromozomální proteiny, nehistonové metabolismus MeSH
- DNA nádorová metabolismus MeSH
- DNA-helikasy genetika metabolismus MeSH
- DNA metabolismus MeSH
- genetické nemoci vrozené genetika metabolismus MeSH
- histony metabolismus MeSH
- jaderné proteiny genetika metabolismus MeSH
- leukemie genetika metabolismus MeSH
- lidé MeSH
- nádory genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- BAZ1B protein, human MeSH Prohlížeč
- chromatin MeSH
- chromozomální proteiny, nehistonové MeSH
- DNA nádorová MeSH
- DNA-helikasy MeSH
- DNA MeSH
- histony MeSH
- jaderné proteiny MeSH
- SMARCA4 protein, human MeSH Prohlížeč
- SWI-SNF-B chromatin-remodeling complex MeSH Prohlížeč
- transkripční faktory MeSH
Inherited disturbances of the mitochondrial energy generating system represent a heterogeneous group of disorders associated with a broad spectrum of metabolic abnormalities and clinical symptoms. We used the polarographic and spectrophotometric method for detection of mitochondrial disorders, because these two techniques provide a different insight into mitochondrial function. In six patients suspected of mitochondrial disease we found defects of complex I (two patients), complex III (one patient), complex IV (two patients) and a combination of defect of complex III and IV (one patient). Citrate synthase activity, used as the reference enzyme, was not changed. A comparison of the two methods showed several differences in evaluation of mitochondrial enzymes activity due to the fact that both methods used different conditions for enzyme activity measurements. In contrast to oxygen consumption measurements, where the function of the whole-integrated respiratory chain is characterized, spectrophotometric measurements characterize activities of isolated complexes in disintegrated membranes. However, it may be concluded from our experiments that both methods provide useful and complementary data about mitochondrial energetic functions. Whereas spectrophotometric data are suitable for evaluation of maximal enzyme activities of mitochondrial enzyme complexes, polarographic data provide better information about enzyme activities in cells with mitochondrial defects under in situ conditions.
- MeSH
- dítě MeSH
- dospělí MeSH
- elektronový transportní řetězec metabolismus MeSH
- genetické nemoci vrozené metabolismus patofyziologie MeSH
- Kearnsův-Sayreův syndrom metabolismus patofyziologie MeSH
- kojenec MeSH
- kosterní svaly enzymologie metabolismus patofyziologie MeSH
- lidé MeSH
- mitochondriální nemoci metabolismus patofyziologie MeSH
- mladiství MeSH
- permeabilita buněčné membrány účinky léků MeSH
- polarografie metody MeSH
- předškolní dítě MeSH
- respirační komplex I metabolismus MeSH
- respirační komplex II metabolismus MeSH
- respirační komplex III metabolismus MeSH
- respirační komplex IV metabolismus MeSH
- spektrofotometrie MeSH
- spotřeba kyslíku účinky léků fyziologie MeSH
- svalové mitochondrie enzymologie metabolismus MeSH
- syndrom MELAS genetika metabolismus patofyziologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- elektronový transportní řetězec MeSH
- respirační komplex I MeSH
- respirační komplex II MeSH
- respirační komplex III MeSH
- respirační komplex IV MeSH
