A review on the status quo and implementation methods of ethics education in standardized training for resident doctors in medical genetics department / 中华医学遗传学杂志

Clinical practice of Medical Genetics involves application of various genetic techniques for the diagnosis of genetic disorders and subsequent genetic counseling and treatment. The principles of Medical Ethics must be fully taken into account when applying genetic knowledge for medical practice. Medical Ethics education is therefore essential for the standardized training of resident doctors in medical genetics department. With a basic system of Medical Genetics Physician Training established, our hospital has made a preliminary exploration for the development of Medical Ethics teaching in resident training through various teaching practices including seminar, network teaching, case study, scene teaching and outpatient teaching, with an aim to strengthen Medical Ethnics knowledge, professionalism and communication skills, and implement Medical Ethics principles throughout clinical practice.

Application of copy number variation sequencing for prenatal diagnosis in women at an advanced maternal age / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation analysis based on next generation sequencing (CNV-seq) in prenatal diagnosis for women at advanced maternal age.@*METHODS@#A prospective analysis was carried out for women who underwent amniocentesis at 18~36 weeks of gestation for fetal CNV-seq for advanced maternal age.@*RESULTS@#For 1461 unrelated Chinese women with a singleton pregnancy, CNV-seq was performed for all samples successfully. The proportion of chromosomal abnormalities was 2.3% (34/1461), of which 44.12% were submicroscopic copy number variations (<5 Mb).@*CONCLUSION@#Pregnant women at an advanced maternal age should be informed for not only common trisomies but all pathogenic chromosomal aberrations. NGS was a sensitive and accurate approach for detecting CNVs.

Evaluation of the practical efficacy of a colloidal gold detection reagent of rabies virus antibody / 中华实验和临床病毒学杂志

Objective@#To evaluate the practical efficacy of a colloidal gold (CG) detection reagent of rabies virus antibody.@*Methods@#Series dilutions of rabies immunoglobulin and serum samples of rabies vaccine immunized population were tested by a CG detection reagent of rabies virus antibody and rapid fluorescent focus inhibition test (RFFIT). The consistency of the qualitative results of rabies virus antibodies between the two methods were compared. The comparison of rates was made by Chi-square test.@*Results@#For rabies immunoglobulin diluent, the detection limit of the rabies virus antibody CG detection reagent was higher than 6.53 IU/ml but lower than 9.53 IU/ml. For the serum samples, the detection limit of the rabies virus antibody CG detection reagent was higher than 2.80 IU/ml but lower than 3.30 IU/ml. The positive rates of serum rabies virus antibodies detected by CG and RFFIT were 26% and 67% respectively, and the difference was statistically significant (χ2 =13.66, P=0.000). The results of RFFIT were regarded as gold standard, false negative results but no false positive results were observed when CG was used to detect serum rabies virus antibodies.@*Conclusions@#The sensitivity of the rabies virus antibody CG detection reagent is poor, and attention should be paid to the phenomenon of missing some practically positive results in practical application of CG detection reagent.

Analysis of DYSF gene mutations in two pedigrees affected with limb-girdle muscular dystrophy type 2B / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze mutations of DYSF gene in two pedigrees affected with limb-girdle muscular dystrophy 2B (LGMD-2B).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of the two probands and unaffected family members. Variant sites were screened by next-generation sequencing using gene panel as well as Sanger sequencing.</p><p><b>RESULTS</b>Four pathogenic mutations of the DYSF gene were detected, which included a de novo mutation and three mutations with uncertain significance. In pedigree 1, the proband carried compound heterozygous mutations of c.1667T to C (p.Leu556Pro) and c.5567T to A (p.Val1856Glu), which were respectively inherited from her mother and father. Proband of pedigree 2 carried compound heterozygous mutations of c.4853A to G (p.Tyr1618Cys) and c.4876G to A (p.Val1612Ile), among which c.4876G to A (p.Val1626Ile) was also found in his father and grandfather, while c.4853A to G (p.Tyr1618Cys) was detected in his mother and grandmother.</p><p><b>CONCLUSION</b>The two compound heterozygous mutations of the DYSF gene probably underlie the LGMD2B in the two pedigrees. Next generation sequencing has conferred great advantage for gene diagnosis of hereditary myopathy.</p>

Application of chromosomal microarray analysis for the diagnosis of children with intellectual disability/developmental delay and a normal karytype / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of children with intellectual disability/developmental delay (ID/DD) but a normal karytype.</p><p><b>METHODS</b>Peripheral blood samples from 92 ID/DD patients were analyzed with CMA using Affymetrix CytoScan 750K arrays. The results were analyzed by ChAS v3.0 software.</p><p><b>RESULTS</b>Eighteen cases (19.57%) were detected with abnormalities by CMA, among which 10 cases were diagnosed with microdeletion/microduplication syndromes. These included 2 Williams-Beuren syndromes, 2 Angelman syndromes, 2 Russell-Silver syndromes, 1 Smith-Magenis syndromes, 1 Wolf-Hirschhorn syndromes, 1 15q26 overgrowth syndrome and 1 Xq28 (MECP2) duplication syndrome. In addition, 8 cases were diagnosed with pathogenic copy number variations (pCNV).</p><p><b>CONCLUSION</b>CMA can significantly improve the diagnostic rate for patients with ID/DD, which is of great value for the treatment of such children and guidance of reproduction for their parents. Therefore, CMA should become the first-line diagnostic test for patients with ID/DD.</p>

Application of chromosomal microarray analysis in prenatal diagnosis for fetal abnormalities detected by ultrasonography / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the outcome of chromosomal microarray analysis (CMA) in prenatal diagnosis for fetal abnormalities detected by ultrasonography.</p><p><b>METHODS</b>Amniotic fluid samples from 477 pregnancies with abnormal ultrasound findings but without common aneuploidies were detected by CMA with Affymetrix CytoScan 750K arrays. The results were analyzed with ChAS v3.0 software.</p><p><b>RESULTS</b>Among the 477 samples, 24 (5.03%) were detected with pathogenic copy number variations (pCNVs) by CMA. Six (9.68%) among 62 cases with structural fetal abnormalities in multiple organ systems were detected with pCNVs, 11 (7.48%) among 147 cases with a single structural anomaly were detected with pCNVs, and 7 (2.61%) among 268 cases with a soft marker were detected with pCNVs.</p><p><b>CONCLUSION</b>CMA has offered a clear advantage over conventional karyotyping for the detection of fetal chromosomal abnormalities, and can provide an effective diagnostic tool for those with one or more structural abnormalities detected by ultrasound.</p>

Analysis of heterozygous duplication of PMP22 gene in a pedigree affected with Charcot Marie Tooth disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze mutation of the PMP22 gene in a pedigree affected with Charcot-Marie-Tooth disease.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of the proband and members from his family, and fetal DNA was extracted from amniotic fluid sample. Multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridization (array-CGH) analyses were carried out to determine the copy number of the PMP22 gene. Sanger sequencing was carried out to detect point mutations of the PMP22 gene.</p><p><b>RESULTS</b>A heterozygous duplication of the PMP22 gene was detected in the proband and his father, while no point mutation, insertion or deletion was found in them. No duplication or deletion of the PMP22 gene was found in other family members.</p><p><b>CONCLUSION</b>Based on clinical symptoms and genetic findings, the heterozygous duplication of the PMP22 gene is probably the cause of the disease in the proband. The fact that the father has carried the same duplication but with no detectable symptom may be due to irregular transmission pattern of the mutation. Genetic counseling for the family should therefore be with caution.</p>

Study of the correlation between NRAMP1 gene polymorphisms and susceptibility to tuberculosis in Tibetan people in Qinghai / 中华微生物学和免疫学杂志

Objective To investigate the correlation between NRAMP1 gene polymorphisms and susceptibility to tuberculosis ( TB) in Tibetan people in Qinghai. Methods A case-control study was con-ducted in this study, involving 99 Tibetan patients with TB and 89 healthy Tibetans. The single nucleotide polymorphisms of NRAMP1 gene at rs17235409 and rs3731865 sites were detected by using TaqMan probe method. Gene cloning and sequencing typing were performed to analyze the single nucleotide polymorphisms of NRAMP1 gene at the rs17235416 site. SPASS20. 0 software was used to statistically analyze the correla-tion between NRAMP1 gene polymorphisms and susceptibility to TB in Tibetan people. Results No signifi-cant difference in the genotype frequencies of rs3731865 and rs17235409 was found between the two groups (χ2=0. 852, P=0. 356;χ2=0. 279, P=0. 597). The genotype frequencies of TGTG/TGTG and TGTG/del+del/del at the rs17235416 site were 70. 7% ( 70/99 ) and 29. 3% ( 29/99 ) in patients with TB and 86. 5% (77/89) and 13. 5% (12/89) in healthy subjects. There were significant differences in the geno-type frequencies of TGTG/TGTG and TGTG/del+del/del between the two groups (χ2=6. 870, P=0. 009). The genotypes of TGTG/del and del/del at rs17235416 were risk factors for TB ( OR=0. 376; 95%CI:0. 178-1. 794 as compared with the TGTG/TGTG genotype in Tibetan people in Qinghai. Conclusion This study suggested that the NRAMP1 gene polymorphisms at rs3731865 and rs1723409 sites had no correlation with the susceptibility to TB in Tibetans in Qinghai. However, the NRAMP1 gene polymorphisms at rs17235416 site were correlated with the susceptibility to TB. The TGTG/del alleles at the rs17235416 site might be the risk factors for tuberculosis in Tibetans in Qinghai.

Application of multiple quantitative fluorescence polymerase chain reaction approach for rapid prenatal diagnosis of common chromosome aneuploidies / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of multiple quantitative fluorescence polymerase chain reaction (QF-PCR) approach for rapid prenatal diagnosis of common chromosomal aneuploidies.</p><p><b>METHODS</b>A total of 4760 amniotic samples from 4649 pregnant women were analyzed with QF-PCR for 21, 18, 13, X and Y aneuploidies, and the results were compared with those of karyotype analysis.</p><p><b>RESULTS</b>The overall success rate for QF-PCR was 98.4%. All the 48 cases of 21, 18, 13, X and Y aneuploidies (including 2 case of 46, XY, rob(13:21), +21; 4 trisomy 21 in 4 twins) were detected by QF-PCR, with the overall sensibility and specificity both reaching 100%. One mosaicism of trisomy 21 and 4 mosaicisms of sex chromosome (1 misdiagnosed by karyotype analysis) were also detected by QF-PCR. Four mosaicisms of sex chromosome were verified as missed diagnosis. All the 64 cases failed by karyotype analysis were successfully analyzed by the QF-PCR approach. The total consistency rate for QF-PCR and karyotyping has reached 98.3%.</p><p><b>CONCLUSION</b>QF-PCR approach can diagnose 21, 18, 13 as well as X and Y aneuploidies within 48 hours, in addition with a portion of mosaicisms. It is an efficient and reliable method for rapid prenatal diagnosis, and therefore provide an important supplement for karyotype analysis.</p>

Studies on the Use of Ultrafiltration in the Preparation of Shengmaiying Oral Liquid / 中草药

Experiments on the use of ultrafiltration in the preparation of Shengmaiying oral liquid were carried out in comparison with the conventional preparation procedure. Results showed that the product obtained had abetter clarity and less impurities. It is postulated that such technique can be used in the purification of many oral liquid preparations of compounded herbal formulations with efficient removal of impurities while retaining the main active principles. The selection of ultrafiltration equipment,its optimum working pressure,temperature and filtration rate were discussed.