Study on clinical features and diagnostic methods of prenatal Wolf-Hirschhorn syndrome / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling.@*METHODS@#We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses.@*RESULTS@#Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb.@*CONCLUSION@#Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

Prenatal diagnosis of five fetuses with 7q11.23 microdeletion or microduplication / 中华医学遗传学杂志

OBJECTIVE@#To investigate the ultrasonographic findings and genetic testing methods for fetuses carrying copy number variants (CNVs) of 7q11.23 region.@*METHODS@#Prenatal cases with 7q11.23 microdeletion/microduplication detected by single nucleotide polymorphism array (SNP array) from January 2016 to June 2020 were retrospectively analyzed, including fetal ultrasound, chromosomal karyotype, SNP array, pregnancy outcome and follow-up. Literature on 7q11.23 CNVs identified upon prenatal diagnosis was also reviewed.@*RESULTS@#Five fetuses were found with 7q11.23 CNVs, including 3 microdeletions and 2 microduplications. Of them, 4 had ultrasonographic anomalies. The karyotypes of all fetuses were normal. Of three 7q11.23 microdeletions, two were de novo, while the remaining one couple did not accept parental verification. Of two 7q11.23 microduplications, one was de novo and the another was inherited from a phenotypic normal father. Three 7q11.23 microdeletions and one de novo 7q11.23 microduplication were electively aborted. One fetus carrying paternally inherited 7q11.23 microduplication was delivered full term. Follow-up found the infant had a normal phenotype.@*CONCLUSION@#Fetuses with 7q11.23 microdeletions or microduplications showed phenotypic heterogeneity. SNP array can accurately detect 7q11.23 CNVs, thereby provide accurate information for prenatal diagnosis and genetic counseling.

Variant analysis for patients from Fujian area with Hong Kong αα type thalassemia / 中华医学遗传学杂志

OBJECTIVE@#To determine the frequency of Hong Kong αα (HK αα) gene in α3.7 positive samples among carriers from Fujian area.@*METHODS@#Routine genetic testing for thalassemia was carried out for 10145 patients with positive screening results. Single PCR and two-round nested PCR were utilized to detect HK αα among 507 patients with α3.7/αα and 2 patients for whom electrophoresis showed α3.7, -αSEA and normal α2 alleles. Reverse dot blot test was used for detecting non-deletional α-thalassemia and β-thalassemia variants.@*RESULTS@#Among the 507 patients with α3.7/αα, HK αα was identified in 35 cases, which included 25 HK αα/αα, 5 HK αα/α3.7, 4 HK αα/αα with heterozygous CD41/42 (HBB: c.126_129delCTTT) variant, 1 HK αα/αα with IVS-II-654 (HBB: c.316_197C>T) heterozygous variant. One patient was confirmed to have α3.7/anti4.2 genotype. The two cases with α3.7, -αSEA and normal α2 alleles were confirmed to be HK αα/--SEA. The frequency of HK αα genotype in Fujian area was therefore 7.27% among patients with α3.7 and 0.36% in the general population.@*CONCLUSION@#A certain proportion of HK αα has been detected in Fujian area, which will enable more accurate diagnosis and genetic counseling.

Analysis of hematological phenotype and genotype of Hb Q-Thailand in Fujian area / 中华医学遗传学杂志

OBJECTIVE@#To explore the hematological phenotype and genotype of hemoglobin Q-Thailand in Fujian area.@*METHODS@#Genomic DNA was extracted from peripheral venous blood samples of patients. Suspected samples were screened by hematological parameters analysis and verified with DNA sequencing.@*RESULTS@#In 35 patients suspected with Hb Q-Thailand, 20 were confirmed, which included one case compounded with heterozygous β mutation and one compounded with Hb New York.@*CONCLUSION@#Analysis of hematological phenotype and genotype of Hb Q-Thailand can faciliate genetic counseling for patients from Fujian area.

Genetic testing and prenatal diagnosis of X-linked ichthyosis in two pedigrees / 中华围产医学杂志

Objective To analyze genetic testing and prenatal diagnosis of two pedigrees with X-linked ichthyosis.Methods Karyotyping,bacterial artificial chromosomes-on-BeadsTM (BoBs),fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) were used to detect amniotic fluid and peripheral blood specimens of two pedigrees,one with and one without known family history of ichthyosis.Clinical data was collected and analyzed as well.Results (1) The pedigree without known family history:Prenatal BoBs showed that the XC1 probe of fetus Ⅳ-12 was from 0.36 to 0.50,suggesting the presence of microdeletion.SNP-array analysis of gravida Ⅲ-13 showed a 1.68 Mb copy number deletion at Xp22.31 and four missing Online Mendelian Inheritance in Man (OMIM) genes (HDHD1,STS,VCX and PNPLA4).Fetal SNP-array revealed a deletion of arr[hg19] Xp22.31 (6 455 151-8 135 644)× 0,indicating a maternally inherited one.FISH analysis verified the deletion in STS gene in fetus Ⅳ-12,whose karyotype was 46,XY.The gravida's female cousin (Ⅲ-21) and nephew (Ⅳ-14) also had STS gene deletion,which size was the same as that from the gravida and the fetus.Fetus (Ⅳ-12) was delivered at term by cesarean section with normal skin,but an extensive white scales appeared on the abdomen one week after birth and the symptom was aggravated when the weather was dry.The infant was followed up to eight months old and no other clinical symptoms were found.(2) The pedigree with known family history:SNP-array revealed that a 1.2 Mb copy number deletion at Xp22.31 and four missing OMIM genes (HDHD1,STS,VCX and PNPLA4) were detected in pregnant women (Ⅲ-21),proband (Ⅳ-16) and fetus (Ⅳ-17).FISH analysis of the fetus verified the deletion in STS gene.The karyotype of the fetus was 46,XY.Fetus Ⅳ-17 was delivered at term by cesarean section with normal skin,but white scales widely appeared on the abdomen ten days after birth.The infant was followed up to four months old and no other clinical symptoms were found.Conclusion Molecular genetic techniques such as BoBs,FISH and SNP array are used in combination in this study to provide genetic testing and prenatal diagnosis to two XLI pedigrees,which is helpful for clinical diagnosis and genetic counseling.

The prevalence and genetic characterization of 22750 cases of beta-thalassemia in Fujian Province / 中华检验医学杂志

Objective To analyze the molecular characterization and prevalence of beta-thalassemia in Fujian Province .Methods RDBwas applied to identify 17 point mutations of beta gene and 3 point mutations of alpha gene .Gap-PCRwas applied to identify 3 deletions of alpha gene , MLPA and DNA sequecing were applied to identify the rare mutational genotype of beta-thalassemia.Results 3515 cases (15.45％)ofβ-thalassemia were confirmed.15 genotypes were found in the studied subjects .βIVS-2-654(C→T)/βN, βCD41-42(-TCTT)/βN, βCD17(A→T)/βN, β-28(A→G)/βN, βCD27-28( +C)/βN, and βCD26(G→A)/βN were the mostcommon genotypes in Fujian Province , accounting for 41.76％, 30.50％, 12.46％, 5.46％, 2.93％and 1.82％respectively , It was found that the total frequency of them was 94.93％in our study.13 cases of deletional β-thalassemia were detected , including 6 cases of Southeast Asia subtype ( SEA-HPFH) , 6 cases of Chinese subtype Gγ(Aγδβ)0 and 1 case of 1.35kb deletion(NG-000007.3:g.69997-71353 del 1357) in one subject .13 cases of rareβ-thalassemia were detected , including Hb J-Bankok in 8 subjects and Hb New York in 5 subjects were diagnosed .Conclusions As a high-risk area forβ-thalassaemia, the detection of deletional β-thalassemia and rare β-thalassaemia subtypes should be screened in addition to the common β-thalassemia genes , so as to demonstrate the results of β-thalassemia gene detection in this region .Those screening results are useful for genetic counseling and can effectively reduce the birth of children with moderate to severe β-thalassaemia .

The observation on the theropeutic effect injected into rat's heptome with ricin and the research in the inhibit of marrow / 介入放射学杂志

Parpose:To observe the therapeutic effects of the ricin's intervention in treating the hepatic carcinoma and to compare the restraint effect to bone manrrow caused by ricin and mitomicin C.Materials and Methods:Use human grafted hepatic carcinoma to naked rat as transplanted rat's liver cancer model.The therapeutic effects of ricin(4?g/kg)were compared with that of lipiodel-emusified riein(8?g/kg)and mitomicin C(500ug/kg)(all the dosages were of the one third of the LD50),with saline injected liver cancers as the control.To observe the tumour's growth inhibition rate,-FP hemogram and marrow change.Results:The growth of turners in group of ricin,lipiodel-emulified ricin,mitomicin C was inhibited,result in tumour necrosis.The inhibition in marrow showed more obvious in mitomicin C than in ricin.The- FP's reduction was significant in comparision with that of the control group,however,there were no remarkable difference among the three drug forms.Conclusion:Ricin has remarkable therapeutic effect on hepatic carcinoma.Ricin's emulsion was stable providing experimentd basis for the toxicity to marrow is clearly lower than mitomicim C

Reversal of multidrug resistance and inhibition of DNA topoisomerase Ⅱ by emulsion of seed oil of Brucea Javanica / 中国药理学通报

AIM To explore the reversal effect of multidrug resistance (MDR) and the influence on topoisomerase (TOPO) activity by emulsion of seed oil of Bbrucea Javanica (ESOBJ) in vitro . METHODS Cytotoxic effects of ESOBJ against sensitive and resistance tumor cells were deter mined by MTT assay. Influences of ESOBJ on the catalytic activities of TOPO Ⅰ and TOPO Ⅱ were measured by TOPO Ⅰ mediated negatively super coiled pBR322 relaxation and TOPOⅡ mediated kDNA decatenation. RESULTS 0 025 g?L -1 of ESOBJ could reverse MDR in various MDR cell lines such as K562/A02?MCF 7/ADM and KB/VCR. DNA TOPO Ⅱ mediated kDNA decatenation experiment showed marked inhibitory action of ESOBJ on TOPO Ⅱ activity at the concentration of 0 31 g?L -1 and TOPO Ⅱ activity was totally inhibited by ESOBJ at the concentration of 2 5 g?L -1 . On the other hand, ESOBJ exhibited no influence on DNA TOPO I mediated pBR322 relaxation and on DNA directly. CONCLUSION ESOBJ could reverse MDR to a certain extent in vitro , and inhibit the activity of TOPO Ⅱ significantly.