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Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
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The use of ion exchange chromatography, gel filtration, and paper electrophoresis for the separation of the peptides obtained by tryptic digestion of the cowpea strain of tobacco mosaic virus protein is described. The amino acid compositions of the 13 tryptic peptides obtained were determined and accounted for 159 residues compared with the 158 found for type tobacco mosaic virus protein. The only tryptic peptide that cowpea tobacco mosaic virus protein and type tobacco mosaic virus protein have in common is asparaginyl-arginine despite the fact that the former is very similar to type tobacco mosaic virus protein in a number of its properties. The amino terminal sequence was found to be acetyl alanyl-tyrosine and the carboxyl terminal sequence was confirmed as alanine preceded by threonine. 相似文献
57.
Liese C.C. Pruitt Zachary J. Kastenberg Stephen J. Fenton Scott S. Short 《Journal of pediatric surgery》2021,56(3):629-631
PurposeExperience with autologous blood patch (ABP) pleurodesis for persistent air leak in the pediatric population is limited. The purpose of this series was to describe the experience with ABP at a single tertiary children's hospital.MethodsA retrospective study was performed of all thoracic procedures done by the pediatric surgery service over three years.ResultsTen patients underwent a total of 17 ABPs. The median age of patients was 12 years (IQR 6–16). The most common underlying reasons for a thoracic procedure included: blebectomy for spontaneous pneumothorax (2), need for lung biopsy (2), resection of known malignant tumor (2), and empyema (2). The median number of days of persistent air leak before first ABP was 7.5 days (IQR 7–10). A second ABP was performed in 6 cases with a third procedure performed in one case. None of the patients developed respiratory compromise during ABP and no infectious complications were identified following ABP.ConclusionsOur cohort demonstrates that ABP for persistent air leak following thoracic surgery is effective with minimal morbidity in children. We believe ABP can be used early and in patients with a broad range of underlying lung pathology. 相似文献
58.
Gene delivery to glioma cells in rat brain by grafting of a retrovirus packaging cell line 总被引:9,自引:0,他引:9
M P Short B C Choi J K Lee A Malick X O Breakefield R L Martuza 《Journal of neuroscience research》1990,27(3):427-439
Retrovirus vectors only integrate into the genome of dividing cells and can thus be used to selectively infect tumor cells in the adult rat brain. Gene delivery was assessed by using the retrovirus BAG vector, which bears the Escherichia coli lacZ gene under the MoMLV LTR promoter-enhancer element, and by histochemical staining for bacterial beta-galactosidase activity. Direct injection of this vector (90-900 cfu) into the adult rat brain, with or without prior inoculation of C6 glioma cells (2 x 10(5) cells) resulted in labeling of only a few cells as assessed 1 week later. When the psi 2-BAG packaging line was grafted into the brain, labeled psi 2-BAG cells could be found after 1 day, but not after 5 days, following grafting, suggesting that the grafted cells had been rejected and that no endogenous cells had integrated released vector, or that expression of lacZ had been turned off. In contrast, when the psi 2-BAG packaging line was grafted into a brain region, which had been inoculated previously with rat C6 glioma cells (2 x 10(5) cells), beta-galactosidase labeling of these tumor cells, identified by immunocytochemistry for glial fibrillary acidic protein and S100, could be demonstrated 10 days later. Thus, grafting of retrovirus packaging lines into adult brain provides a mean to infect tumor cells in situ. The grafted packaging cells may continue to release retrovirus particles for an extended period, thus infecting more cells at the stage of division appropriate for viral integration, as compared to inoculation of the virus alone. Grafting of retrovirus packaging cell lines could be used to selectively deliver "killer" or "suppressor" genes to tumor cells in the brain to curtail their growth. 相似文献
59.
一年级工科大学生艾滋病/性病同伴教育的近期效果研究 总被引:16,自引:9,他引:7
为探讨在一年级工科大学生中开展预防艾滋病、性病同伴教育的可行性,1998 年10- 11 月,在某工科大学整群抽样选取183 人为干预组,207 人为内对照组;在另一所工科大学一年级抽取207 人为外对照组。对干预组实施预防艾滋病、性病同伴教育,通过教育前后两次问卷进行近期效果评价。结果表明,干预组在教育后艾滋病、性病知识均分及问题答对率均有大幅度提高,与内、外对照组比较差异有高度显著性( P< 0-01),而内、外对照组提高不明显。提示在一年级工科学生中开展艾滋病/ 性病/ 安全性行为同伴教育是可行而有效的 相似文献
60.
Bolster DR Trappe SW Short KR Scheffield-Moore M Parcell AC Schulze KM Costill DL 《Medicine and science in sports and exercise》1999,31(2):251-257
PURPOSE: The purpose of this study was to examine the effect of a decreased body core temperature before a simulated portion of a triathlon (swim,15 min; bike, 45 min) and examine whether precooling could attenuate thermal strain and increase subjective exercise tolerance in a warm environment (26.6 degrees C/60% relative humidity (rh)). METHODS: Six endurance trained triathletes (28+/-2 yr, 8.2+/-1.7% body fat) completed two randomly assigned trials 1 wk apart. The precooling trial (PC) involved lowering body core temperature (-0.5 degrees C rectal temperature, Tre) in water before swimming. The control trial (CON) was identical except no precooling was performed. Water temperature and environmental conditions were maintained at 25.6 degrees C and 26.6 degrees C/60% rh, respectively, throughout all testing. RESULTS: Mean time to precool was 31+/-8 min and average time to reach baseline Tre during cycling was 9+/-7 min. Oxygen uptake (VO2), HR, skin temperature (Tsk), Tre, RPE, and thermal sensation (TS) were recorded following the swim segment and throughout cycling. No significant differences in mean body (Tb) or Tsk were noted between PC and CON, but a significant difference (P < 0.05) in Tre between treatments was noted through the early phases of cycling. No significant differences were reported in HR, VO2, RPE, TS, or sweat rate (SR) between treatments. Body heat storage (S) was negative following swimming in both PC (-92+/-6 W x m2) and CON (-66+/-9 W x m2). A greater S occurred in PC (109+/-6 W x m2) vs CON (79+/-4 W x m2) during cycling (P < 0.05). CONCLUSIONS: Precooling attenuated the rise in Tre, but this effect was transient. Therefore, precooling is not recommended before a triathlon under similar environmental conditions. 相似文献