Study of the phenylalanine hydroxylase gene variants in patients with phenylketonuria from Jiangxi province / 中华医学遗传学杂志

Objective@#To delineate the variants spectrum of phenytalanine hydroxylase (PAH) gene among 78 unrelated patients with phenylketonuria (PKU) from Jiangxi province.@*Methods@#The 13 exons and flanking intronic regions of the PAH gene were subjected to PCR amplification and sequencing.@*Results@#A total of 143 variants were detected among the 156 alleles, which included 54 types of variants, which yielded a detection rate of 91.7%. Common variants have included R243Q (26/143, 18.2%), R408Q (10/143, 7.0%), EX6-96A>G (8/143, 5.6%), IVS4-1G>A (7/143, 4.9%), R241C (7/143, 4.9%) and V399V (7/143, 4.9%). In addition, 6 novel variants were detected, which included IVS4-3T>G, Q172H, C284Y, V291L, V329del, and L430R. The variants consisted of missense, splicing, nonsense and deletion variants, which have mainly located in exons 7 (45, 31.5%), 12 (17, 11.9%), 11 (16, 11.2%) and 6 (14, 9.8%).@*Conclusion@#Variants of the PAH gene identified in Jiangxi province mainly involve exons 7, 12, 11 and 6, with the most common variants being R243Q and R408Q. Six novel variants were identified.

Study of the phenylalanine hydroxylase gene variants in patients with phenylketonuria from Jiangxi province / 中华医学遗传学杂志

OBJECTIVE@#To delineate the variants spectrum of phenytalanine hydroxylase (PAH) gene among 78 unrelated patients with phenylketonuria (PKU) from Jiangxi province.@*METHODS@#The 13 exons and flanking intronic regions of the PAH gene were subjected to PCR amplification and sequencing.@*RESULTS@#A total of 143 variants were detected among the 156 alleles, which included 54 types of variants, which yielded a detection rate of 91.7%. Common variants have included R243Q (26/143, 18.2%), R408Q (10/143, 7.0%), EX6-96A to G(8/143, 5.6%), IVS4-1G to A(7/143, 4.9%), R241C(7/143, 4.9%) and V399V(7/143, 4.9%). In addition, 6 novel variants were detected, which included IVS4-3T to G, Q172H, C284Y, V291L, V329del, and L430R. The variants consisted of missense, splicing, nonsense and deletion variants, which have mainly located in exons 7 (45, 31.5%), 12(17, 11.9%), 11(16, 11.2%) and 6(14, 9.8%).@*CONCLUSION@#Variants of the PAH gene identified in Jiangxi province mainly involve exons 7, 12, 11 and 6, with the most common variants being R243Q and R408Q. Six novel variants were identified.

Genetic analysis and prenatal diagnosis for a pregnant woman with an unbalanced t(1;2), t(6;7) translocation and intellectual disability / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide genetic analysis for a pregnant woman with chromosomal translocations and intellectual disability, and to provide prenatal diagnosis for her fetus.</p><p><b>METHODS</b>Routine G-banding was performed to analyze the karyotypes of the woman and her fetus. Copy number variants were determined with array comparative genomic hybridization (array-CGH).</p><p><b>RESULTS</b>The pregnant woman has carried an apparently balanced translocation involving chromosomes 1, 2, 6 and 7, with a karyotype of 46, XX, t(1;2) (p22;p23), t(6;7) (q21;p15). The karyotype of her fetus was ascertained as 46, XY, t(6;7) (q21;p15) mat. Array-CGH has detected a 4 Mb microdeletion at 6q22.1-q22.31 (115 311 507-119 332 956) in both individuals. As the 6q22.1-q22.31 microdeletion may be associated with the main clinical manifestations of the woman, the family decided to terminate the pregnancy. The fetus was male and appeared to have no obvious abnormality.</p><p><b>CONCLUSION</b>Prenatal diagnosis for pregnant women with translocations and mental retardation is a challenging task. Combined application of cytogenetic analysis and array-CGH may facilitate the diagnosis and genetic counseling.</p>

Application of BoBs technique for detecting common chromosome microdeletion and microduplication syndromes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities.</p><p><b>METHODS</b>Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH).</p><p><b>RESULTS</b>Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH.</p><p><b>CONCLUSION</b>BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.</p>

Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs / 中华妇产科杂志

Objective To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. Methods From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. Results Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs;while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. Conclusion Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.

Feasibility study of transplantation of penile corpus cavernosum and major pelvic ganglion in renal subserous region / 北京大学学报(医学版)

Objective:To study the feasibility of transplantation of normal rat penile corpus cavernosum and major pelvic ganglion (MPG)into the renal subserous region of a Nu /Nu mouse based on allograft technology.Methods:Penile corpus cavernosum and MPG,harvested from Sprague-Dawley (SD)rats under sterile condition,were transplanted underneath the kidney capsule of Nu /Nu mice through the mi-crosurgery instruments and surgery microscope.The histopathologic changes and cellular proliferation in the transplanted penile corpus cavernosum and MPG were then analyzed at the end of 1week and 4 weeks after transplantation.Histological staining and immunohistochemical staining were used to evaluate the main outcome measures.Results:After 1 week,the tissue morphology of the transplanted corpus caverno-sum underneath the kidney capsule of Nu /Nu mice was consistent with normal penile corpus cavernosum, and blood could be observed in the penis cavernous sinus of the graft;after 4 weeks,the mophorlogy of the tranplanted corpus cavernosum near the kidney was consistent with normal penile corpus cavernosum, while fibrosis was noteworthy in the graft away from the kidney,but blood could still be seen in the penis cavernous sinus.After 1 week,the tissue morphology of the transplanted MPG was consistent with normal MPG,multiple islet-like cell clusters could be seen in the transplanted MPG in the renal subserous re-gion,and angiogenesis could be observed near the kidney;after 4 weeks,a network of blood vessels was clearly visible away from the kidney,and islet-like cell clusters were still clearly observed in the trans-planted MPG.In addition,ki67 positive cells were observed in the transplanted penile corpus cavernosum and MPG after 4 weeks of transplantation,which indicated that there was still cell proliferation activity in the grafts.Conclusion:The transplanted corpus cavernosum and MPG underneath the kidney capsule of Nu /Nu mice could survive at least 4 weeks.Moreover,the inner structure of the transplanted corpus ca-vernosum and MPG was close to the normal tissue.The underlining mechanism may be related to the lo-cal microenvironment underneath the kidney capsule of Nu /Nu mice and the neovascularization in the transplanted grafts.

Genetic analysis and prenatal diagnosis of Xp deletion in a family with Duchenne/Becker muscular dystrophy / 中华医学遗传学杂志

OBJECTIVE To delineate a deletional mutation of the Dystrophin gene on the short arm of chromosome X in a family affected with Duchenne/Becker muscular dystrophy. METHODS G-banded karyotyping, multiple ligation probe amplification (MLPA), array-based comparative genomic hybridization(array-CGH) and whole genome exon high-throughput sequencing were employed to delineate the mutation in the family. RESULTS GTG banding has demonstrated deletion of the terminal part of the short arm of chromosome X in the fetus. The same deletion was also found in its mother and maternal grandmother. MLPA analysis has revealed removal of exons 52 to 79 of the Dystrophin gene. A 30 Mb deletion in Xp22.33-p21.1 and a 10 Mb duplication in Xq27.2-q28 were identified by array-CGH and whole genome exon high-throughput sequencing. CONCLUSION The Xp deletion has led to deletion of exons 52 to 79 of the Dystrophin gene in the family. The female carriers also had certain features of Turner syndrome due to the same deletion.

Effect of PM10 in Moxa Smoke on Apoptosis of Human Lung Adenocarcinoma Cell Line-A549 Cells / 中国中医药信息杂志

Objective To observe the effect of PM10 (inhalable particles) in moxa smoke on apoptosis of human lung adenocarcinoma cell line-A549 cells, and explore the possible mechanisms of inducing apoptosisMethods The A549 cells were studied in vitro experiment method, which were stained by Hoechest33258 staining method. Their morphological changes of apoptosis were observed by the fluorescence microscopy. The levels of intracellular Ca2+ and reactive oxygen species (ROS), and expression of NF-κB p65 were also measured.Results Some apoptotic cells were observed after treated with moxa smoke PM10 in the concerntration of 400μg/mL. After 4 hours intervention by moxa smoke PM10 in A549 cells, the intracellular Ca2+ level increased significantly (P0.05). Compared with the blank control group, ROS level was significantly lower (P<0.05) in A549 cells after intervention of moxa smoke PM10.Conclusion PM10 in moxa smoke could induce apoptosis of A549 cells, could increase cytosolic Ca2+ level.

Retrospection,stratagem,and practice on innovative drug research and development of Chinese materia medica / 中草药

Taking the national key scientific and technological project in 11th Five-year and 10th Five-year Plan as its main clue,the innovative Chinese materia medica(CMM)research course has been reviewed in this paper.Based on the enlightenment from the first herbal medicine VeregenTM,which has been approved by FDA,together with the study and comprehension of many great achievements of new drug research,the strategy of innovative CMM research and development(R&D)and its practical route is going to be put forward in this article.With the innovative Compound Prescription of CMM research as the main innovative approach,innovation can be realized by the following three aspects:New substances,including new compound,new effective fraction/group or new components and their combinations;new indication of known compounds or extracts;the secondary development of high-quality Chinese patent medicine.Besides,in order to support the R & D of original drugs with Chinese characteristics,the international experiences in target-dependent screening and evaluation and optimization of leading compounds based on clinical application should be referenced,and the mechanism and targets of traditional Chinese medicine by genetic and molecular level be clarified.