Clinical value of different genetic testing methods for detection of true fetal chromosome mosaicism / 中华围产医学杂志

Objective:To investigate the performance of chromosome karyotype, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in prenatal diagnosis of true fetal chromosome mosaicism. Methods:This retrospective study enrolled 40 women with true fetal chromosome mosaicism from 4 071 singleton pregnant women who were indicated for and underwent amniocentesis or/and cordocentesis in the the First Affiliated Hospital of Sun Yat-sen University from April 2018 to August 2021. The results of chromosome karyotyping, CMA and FISH, the types of chromosomal mosaicism, mosaicism ratio and pregnancy outcomes were analyzed using Chi-square test. Results:(1) The detection rate of true fetal mosaicism was 0.98% (40/4 071). (2) Sex chromosome mosaicism accounted for 42.5% (17/40). Other chromosomal mosaicism involved chromosomes 21, 22, 18, 16, 7, 12, 15, 17 and 20, as well as balanced chromosomal translocation. (3) The detection rate of true fetal mosaicism by chromosome karyotyping was 77.4% (24/31) from amniotic fluid samples and 10/19 from umbilical cord blood samples, while that data by CMA was 76.7% (23/30) and 7/11,respectively. (4) Of the 40 pregnant women with fetal chromosome mosaicism, FISH test was performed on 20 cases (14 cases were verified with both amniotic fluid and umbilical cord blood samples, five with amniotic fluid samples and one with umbilical cord blood sample), and all of the diagnosis of mosaicism were confirmed. For those with mosaicism ratio <30%, the detection rate by FISH was higher than that by CMA among amniotic fluid samples [14/19 vs 43.5% (10/23), χ2=3.88, P=0.049]. (5) Among the 40 pregnant women, five were lost to follow-up; 18 chose to terminate the pregnancy; and 17 continued the pregnancy to delivery. No abnormalities in mental or physical development were reported in the 17 neonates after birth or during on-line follow-up between 6 to 24 months old. Of the 14 pregnant women with mosaicism ratio <30% which confirmed by FISH, eight chose to continue the pregnancy, and no abnormalities in mental development or growth were found in the neonates. Conclusions:In prenatal diagnosis of true fetal choromosome mosaicism, the incidence of sex chromosome mosaicism is the highest. FISH may improve the prenatal diagnosis rate of mosaicism and is more accurate in determining the mosaicism ratio. The combination of FISH, CMA and chromosome karyotyping would significantly improve the detection rate of chromosomal mosaicism and assess the mosaicism ratio more accurately, which is of great value in clinical consultation and evaluation of fetal prognosis.

Prenatal genetic features and prognostic factors in monochorionic twins with twin reversed arterial perfusion sequence / 中华围产医学杂志

Objective:To investigate the prenatal genetic features and the factors influencing the prognosis of twin reversed arterial perfusion sequence (TRAPS) in monochorionic twin pregnancies.Methods:A total of 99 cases diagnosed with TRAPS by prenatal ultrasound in the First Affiliated Hospital of Sun Yat-sen University from July 1, 2007, to December 31, 2021, were included retrospectively. The prenatal genetic features of acardiac and pump twins were analyzed. Eighty-nine cases were followed up and divided into two groups: the expectation group ( n=45) and the intrauterine intervention group (all underwent radiofrequency ablation, n=44) and the pregnancy outcomes were compared between the two groups. After excluding eight cases without complete ultrasound data, the expectation group was further divided into two subgroups: the pump fetus survival ( n=28) and the pump fetus death groups ( n=9), and the survival subgroup was divided into the spontaneous arrest group ( n=16) and coexistence group ( n=12) according to whether or not the blood flow stopped spontaneously.The relationship between ultrasonic indexes and pregnancy outcome was compared between the groups. Chi-square test (or Fisher's exact test), univariate logistic regression analysis and receiver operating characteristic (ROC) curve were used to analyze the relationship between the estimated acardiac to pump twin weight ratio (A/P Wt) and the pregnancy outcome of the pump twin in the expectation group. Results:(1) The median gestational age at diagnosis of the 99 TRAPS cases was 16.4 weeks (13.3- 21.3 weeks) and 32% (32/99) were diagnosed in the first trimester. Most of the cases were monochorionic diamniotic pregnancies (72/99, 73%). The survival rate of the pump twins was 71% (63/89). (2) Chromosome karyotyping and/or chromosomal microarray analysis was performed in 19 acardiac twins and 82 pump twins. The detection rate of genetic abnormalities in the acardiac twins was higher than that in the pump twins [4/19 vs 5% (4/82), Fisher's exact test, P=0.039]. Chromosomal microarray analysis was performed in 54 pump twins with normal karyotypes and the results showed three (6%) with genetic abnormalities. (3) In the expectation group, the area under ROC curve for the prenatal A/P Wt were 0.913 in predicting pump twin death and 0.807 in predicting spontaneous cessation of blood flow in the cardiac twin, and the cut-off values were 0.24 (sensitivity: 88.9%, specificity: 96.4%) and 0.11 (sensitivity: 75.0%, specificity: 81.3%), respectively. The survival rate of pump twins with abnormal cardiac function after intrauterine intervention was higher than that of the expectant group [72% (18/25) vs 3/11, Fisher's exact test, P=0.025]. Conclusions:TRAPS can be diagnosed in the first trimester and commonly occur in monochorionic diamniotic pregnancies. The detection rate of genetic abnormalities in the acardiac twins is higher than that in the pump twins. Prenatal A/P Wt>0.24 indicates the death of the pump twin and prenatal A/P Wt≤0.11 suggests a high possibility of spontaneous cessation of blood flow in the acardiac twin. Radiofrequency ablation is an effective method for improving the prognosis of the pump twin with cardiac dysfunction.

Clinical and genetic analysis of a patient with 17-hydroxylase/17,20-lyase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency.@*METHODS@#The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members.@*RESULTS@#Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant.@*CONCLUSION@#Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

A consensus recommendation for the interpretation and reporting of copy number variation and regions of homozygosity in prenatal genetic diagnosis / 中华医学遗传学杂志

Chromosomal microdeletions and microduplications have been proven to be a significant proportion of genetic factors underlying birth defects. Chromosomal microarray analysis (CMA) and next generation sequencing-based copy number variation (CNV-seq) assay have been recommended as first-tier tests for prenatal evaluation of disease-causing CNV across the genome. With the broad application of such technologies in prenatal genetic diagnosis, there is a needed to enhance the consistency in interpretation and reporting of CNV results in clinical laboratories across China. In addition, a standard guideline for prenatal analysis and reporting of regions of homozygosity (ROH) is also required. To assist the classification, interpretation and reporting of CNV/ROH, the following recommendations have been developed, which may enhance a standard application of CMA/CNV-seq techniques in prenatal genetic diagnosis.

Analysis of a pedigree with partial trisomy 9 and partial monosomy 13 derived from a maternal balanced t(9;13) translocation / 中华医学遗传学杂志

OBJECTIVE@#To determine the nature and origin of aberrant chromosomes in a child with multiple anomalies and psychomotor retardation.@*METHODS@#Routine G-banding was carried out to analyze the karyotypes of the patient and his parents, and next generation sequencing for copy number variations (CNV-seq) was used for the fine mapping of the aberrant chromosomal regions.@*RESULTS@#The proband and his uncle exhibited psychomotor retardation, craniofacial malformation, infantile external genitalia, and concealed penis. Cytogenetic analysis indicated that the child has a 46,XYqh+,+(9),t(9;13)(q13;q12),pat,-13 karyotype. His uncle was XYqh+,+(9),t(9;13)(q13;q12)mat,-13, his father was 46,XYqh+,t(9;13)(q13;q12)mat, his grandmother was 46,XX,t(9;13)(q13;q12), and his grandfather was 46,XYqh+. The result of CNV-seq assay for the child was 46,XY,+9p(pter-p13.2,-40 Mb×3). No deletion was detected.@*CONCLUSION@#The partial trisomy 9 and partial monosomy 13 probably underlie the phenotypic abnormalities in the child. Combined chromosomal karyotyping and DNA sequencing can facilitate delineation of the nature and origin of the aberrant chromosomes.

Prenatal genetic analysis of two fetuses with Miller-Dieker syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform molecular cytogenetic study on two fetuses with abnormal ultrasound findings and analyze their genotype-phenotype correlation.</p><p><b>METHODS</b>G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on amniotic fluid cells from both fetuses and peripheral blood samples from their parents. Results of SNP array were analyzed with bioinformatics software.</p><p><b>RESULTS</b>G-banded karyotyping failed to detect any abnormalities in both fetuses and their parents. SNP array detected a 2.484 Mb terminal deletion at 17p13.3 [arr[hg19] 17p13.3 (83 035-2 567 405)×1] in fetus 1 and a 3.295 Mb terminal deletion at 17p13.3p13.2 [arr[hg19] 17p13.3p13.2 (83 035- 3 377 560)×1] in fetus 2. Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin. Metaphase FISH performed on amniotic fluid cells confirmed the presence of 17p13.3 and 17p13.3p13.2 deletions detected by the SNP array, while metaphase FISH performed on the parents excluded any potential chromosome rearrangements.</p><p><b>CONCLUSION</b>Abnormal ultrasound features for fetuses with MDS mainly include central nervous system anomalies. SNP array can efficiently detect 17p13.3 microdeletions underlying MDS, and accurately map the breakpoints and involved genes, which may facilitate understanding of the genotype and phenotype correlations for MDS.</p>

Phenotypic and genotypic analysis of a fetus carrying an intermediate 22q11.2 deletion encompassing the CRKL gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the phenotypic characteristics of 22q11.2 deletion syndrome and the role of CRKL gene in the pathogenesis of cardiac abnormalities.</p><p><b>METHODS</b>G-banded karyotyping, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization (FISH) were performed on a fetus with tetralogy of Fallot detected by ultrasound. Correlation between the genotype and phenotype was explored after precise mapping of the breakpoints on chromosome 22q11.2. SNP array was also performed on peripheral blood samples from both parents to clarify its origin.</p><p><b>RESULTS</b>The fetus showed a normal karyotype of 46,XY. SNP array performed on fetal blood sample revealed a 749 kb deletion (chr22: 20 716 876-21 465 659) at 22q11.21, which encompassed the CRKL gene but not TBX1, HIRA, COMT and MAPK1. Precise mapping of the breakpoints suggested that the deleted region has overlapped with that of central 22q11.2 deletion syndrome. SNP array analysis of the parental blood samples suggested that the 22q11.21 deletion has a de novo origin. The presence of 22q11.21 deletion in the fetus was also confirmed by FISH analysis.</p><p><b>CONCLUSION</b>Central 22q11.21 deletion probably accounts for the cardiac abnormalities in the fetus, for which the CRKL gene should be considered as an important candidate.</p>

Genetic study of a fetus with 9p direct duplication deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To use next generation sequencing (NGS) to identify unknown abnormality of chromosome 9 in a fetus and explore its mechanism.</p><p><b>METHODS</b>A pregnant woman with abnormal fetal ultrasound finding underwent amniocentesis for G-banded chromosomal analysis. Karyotyping was also performed on peripheral blood samples derived from its parents. Fetal blood sample was obtained for NGS testing to identify abnormality unrecognized by karyotyping.</p><p><b>RESULTS</b>Analysis of amniocytes has revealed a 46,XX,der(9)(?::p21 to qter) karyotype, while both parents had a normal karyotype. NGS analysis of the fetus revealed a 20.67 Mb duplication (4 454 279-25 126 275) at 9p21.3p24.2, which overlapped with that of the 9p duplication syndrome, and a 4.43 Mb deletion at 9p24.2p24.3 (10 001-4 442 364), which partially overlapped with that of 9p deletion syndrome and 46,XY sex reversal 4 region. Comparison of the sequencing data with reference genome database indicated direct duplication of 9p21.3p24.2, which was also supported by review of the morphology of chromosome 9p. Therefore, the karyotype of the fetus was verified to be 46,XX,der(9) dir dup(9)(p21.3p24.2), del(9)(p24.2p24.3).</p><p><b>CONCLUSION</b>Combined G-banded karyotyping and NGS can identify dir dup del(9p) with accuracy. Delineation of the mechanism of dir dup del(9p) and its genotype-phenotype correlation may facilitate genetic counseling and estimation of recurrence risk.</p>

Unexpected discovery of a fetus with DMD gene deletion using single nucleotide polymorphism array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the value of single nucleotide polymorphism array (SNP array) for the identification of de novo mutations in the DMD gene among fetuses.</p><p><b>METHODS</b>G-banded karyotyping and SNP array were performed on a fetus with intrauterine growth restriction but without family history of Duchenne/Becker muscular dystrophy (DMD/BMD). Multiplex ligation-dependent probe amplification (MLPA) was subsequently applied on amniocytes and maternal peripheral blood sample to detect DMD gene deletion/duplication mutations.</p><p><b>RESULTS</b>Karyotyping of amniocytes showed a normal 46, XY karyotype. SNP array on amniocytes detected a 116 kb deletion (chrX: 32 455 741-32 571 504) at Xp21.1 with breakpoints at introns 16 and 30 respectively, encompassing exons 17-29 of the DMD gene. In addition, MLPA analysis of the DMD gene on amniocytes confirmed the deletion of exons 17 to 29 identified by SNP array. However, no deletion/duplication mutation was detected by MLPA in the mother.</p><p><b>CONCLUSION</b>The de novo deletion of exons 17 to 29 of the DMD gene detected in the fetus may result in BMD or DMD. SNP array can improve the efficiency for detecting genomic disorders in fetuses with unidentified pathogenic genes, negative family history and nonspecific phenotypes.</p>

Prenatal genetic diagnosis for a fetus with atypical neurofibromatosis type 1 microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the correlation between atypical neurofibromatosis type 1(NF1) microdeletion and fetal phenotype.</p><p><b>METHODS</b>Fetal blood sampling was carried out for a woman bearing a fetus with talipes equinovarus. G-banded karyotyping and single nucleotide polymorphism array (SNP-array) were performed on the fetal blood sample. Fluorescence in situ hybridization (FISH) was used to confirm the result of SNP array analysis. FISH assay was also carried out on peripheral blood specimens from the parents to ascertain the origin of mutation.</p><p><b>RESULTS</b>The karyotype of fetus was found to be 46, XY by G-banding analysis. However, a 3.132 Mb microdeletion was detected in chromosome region 17q11.2 by SNP array, which overlaped with the region of NF1 microdeletion syndrome. Analyzing of the specimens from the fetus and its parents with FISH has confirmed it to be a de novo deletion.</p><p><b>CONCLUSION</b>Talipes equinovarus may be an abnormal sonographic feature of fetus with atypical NF1 microdeletion which can be accurately diagnosed with SNP array.</p>

Genetic analysis of a fetus with partial 1q monosomy and partial 17q trisomy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a fetus with abnormal sonographic features and correlated its genotype with phenotype.</p><p><b>METHODS</b>G-banding analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed for the fetus. Karyotyping and FISH were also carried out for the parents.</p><p><b>RESULTS</b>SNP array detected a 4.4 Mb deletion at 1q44 and a 10.4 Mb duplication at 17q24.3q25.3 in the fetus. Based on the results of SNP array and FISH analysis, the father was diagnosed with a cryptic t(1;17)(q44;q24.3) translocation. The fetus has inherited a der(1)t(1;17)(q44;q24.3) from its father.</p><p><b>CONCLUSION</b>The 1q44 deletion and 17q24.3q25.3 duplication may have contributed to the abnormal sonographic features presented by the fetus.</p>

Prenatal diagnosis of 1p36.3 microdeletion in a fetus with complex heart defect / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a fetus presenting with complex heart defect and assess the recurrence risk.</p><p><b>METHODS</b>Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism-based array (SNP-array) were used to analyze the fetus and his parents.</p><p><b>RESULTS</b>SNP-array has detected a 6.9 Mb microdeletion at 1p36.33-p36.23 in the fetus. Chromosomal and FISH analyses indicated that the father of the fetus had a karyotype of 46,XY,t(1;14)(p36.3;p12), and that the fetus has inherited an abnormal chromosome 1 derived from the paternal translocation.</p><p><b>CONCLUSION</b>SNP-array combined with GTG banding and FISH can help to detect cryptic translocation, microdeletion or microduplication of chromosomes and is valuable to assess the recurrence risk for the affected family.</p>

Application of single nucleotide polymorphism-based array analysis for prenatal diagnosis of a fetus with de novo derivative chromosome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a fetus with increased nuchal translucency and nuchal fold, and to assess the recurrence risk for her family and provide a basis for prenatal diagnosis.</p><p><b>METHODS</b>G-banded karyotyping and single nucleotide polymorphism-based array (SNP-Array) analysis were used to analyze the fetus and her parents.</p><p><b>RESULTS</b>SNP-Array analysis has detected a 41.04 Mb duplication at Xp22.33p11.4 and a 30.51 Mb duplication at 13q31.3q34 in the fetus. G-banding karyotyping indicated that the fetus had a karyotype of 46,X,der(X)(13qter-13q31::Xp11.4-Xp22.3::Xp22.3-Xqter). Her parents had normal results for both G-banding karyotyping and SNP-Array analysis, suggesting that the fetus has carried a de novo derivative chromosome X.</p><p><b>CONCLUSION</b>SNP-Array combined with G-banding karyotyping is helpful to confirm the composition and connection type of de novo derivative chromosome, which can improve the accuracy of diagnosis and is valuable for the evaluation of recurrence risk.</p>

Accurate detection of a case with Angelman syndrome (type 1) using SNP array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a case with Angelman syndrome (AS) using single nucleotide polymorphism array (SNP array) and explore its genotype-phenotype correlation.</p><p><b>METHODS</b>G-banded karyotyping and SNP array were performed on a child featuring congenital malformations, intellectual disability and developmental delay. Mendelian error checking based on the SNP information was used to delineate the parental origin of detected abnormality. Result of the SNP array was validated with fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>The SNP array has detected a 6.053 Mb deletion at 15q11.2q13.1 (22,770,421- 28,823,722) which overlapped with the critical region of AS (type 1). The parents of the child showed no abnormal results for G-banded karyotyping, SNP array and FISH analysis, indicating a de novo origin of the deletion. Mendelian error checking based on the SNP information suggested that the 15q11.2q13.1 deletion was of maternal origin.</p><p><b>CONCLUSION</b>SNP array can accurately define the size, location and parental origin of chromosomal microdeletions, which may facilitate the diagnosis of AS due to 15q11q13 deletion and better understanding of its genotype-phenotype correlation.</p>

Confirmation of a maternal cryptal balanced translocation through analysis of a fetus using microarray / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a fetus with heart defects and to assess the recurrence risk for her family.</p><p><b>METHODS</b>Single nucleotide polymorphism-based arrays (SNP-Array) analysis using Affymetrix Genome Wide Human SNP CytoHD was performed to analyze the fetus and her parents. Karyotype analysis was also carried out.</p><p><b>RESULTS</b>SNP-Array has detected a 14.5 Mb duplication at 9p and a 14.7 Mb deletion at 11q. Karyotype analysis indicated that the fetus' mother has a karyotype of 46, XX, t(9;11) (p23;q24). Therefore, the fetus has inherited a derivative chromosome 11 derived from the maternal translocation, and her karyotype was 46, XX, der(11) t(9;11) (p23;q24) mat.</p><p><b>CONCLUSION</b>SNP-Array combined with high resolution GTG banding has confirmed that the fetus has a derivative chromosome 11 derived from her mother's balanced translocation, resulting in partial 9p trisomy and partial 11q monosomy. This couple therefore have a high recurrence risk. SNP-Array is capable of detecting small chromosomal imbalance in abnormal fetuses and can pinpoint the breakpoints. It therefore has the advantage for the detection of unbalanced translocation which is difficult to detect with GTG banding, which is important for assessment the recurrence risk for cryptic balanced translocation carriers.</p>

Prenatal diagnosis of five cases of monochorionic-diamniotic twins discordant for karyotype analysis / 中华医学遗传学杂志

OBJECTIVE To explore the mechanism and diagnostic method for monochorionic-diamniotic twins discordant for karyotype analysis. METHODS Dual amniocentesis was performed on five pairs of monochorionic-diamniotic twins, which all consisted of a normal twin and one with multiple malformations revealed by ultrasound. Karyotype analysis was performed on amniocytes derived from each of the twins. Zygosity was also determined with DNA extracted from amniocytes with 16 polymorphic microsatellite markers. RESULTS Three cases of 45,X, one case of 47,XX,+9 and one case of 47,XY,+18 were detected among the abnormal twins, while the normal fetuses all had a normal karyotype. DNA analysis suggested that, in all cases, the twins have shared the 16 polymorphic microsatellite markers, which confirmed their monozygosity. CONCLUSION Monochorionic-diamniotic twins may be discordant for karyotyping, for which anaphase lagging, chromosomal non-disjunction and trisomy rescue may be the underlying reasons. As a simple method, dual amniocentesis can be used to obtain amniotic fluid samples for karyotype analysis and determination of zygosity for such twins.

Chromosomal microarray analysis for lateral ventriculomegaly in fetus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between fetal lateral ventriculomegaly and chromosomal microarray analysis (CMA) abnormalities.</p><p><b>METHODS</b>Fifty fetuses with lateral ventriculomegaly detected by ultrasound and a normal karyotype were included. Forty four fetuses were classified as mild ventriculomegaly (MVM), in which the lateral ventricular atrium was 10-15 mm. Six had severe ventriculomegaly (SVM), with the lateral ventricularatrium being ≥ 15 mm. The fetuses were also divided into isolated (n= 21) and non-isolated groups (n= 29) based on whether they are associated with other anomalies.</p><p><b>RESULTS</b>Thirteen (26%) of the fetuses were found to be abnormal by CMA. For the 44 cases with MVM, 9 (20.9% ) were found to be abnormal, while for the 6 cases with SMV, 4 (66.7%) were found to be abnormal (P>0.05). CMA abnormalities were found in 2 (9.5%) of the 21 fetuses with isolated ventriculomegaly group and 11 (37.9%) of the 29 fetuses with non-isolated ventriculomegaly group (P<0.05).</p><p><b>CONCLUSION</b>Chromosome microdeletions and microduplications are the most common abnormalities found in fetal lateral ventriculomegaly. When ventriculomegaly is associated with other anomalies, the incidence of CMA abnormally is much higher. Prenatal diagnosis is necessary for fetuses with lateral ventriculomegaly.</p>

A clinical observation on correlations between glycosylated hemoglobin level and traditional Chinese medicine syndrome differentiations in young and middle-aged type 2 diabetic patients with heart failure and preserved ejection fraction / 中国中西医结合急救杂志

Objective To investigate traditional Chinese medicine (TCM) syndrome differentiations and glycosylated hemoglobin (HbA1c) levels in the young and middle-aged type 2 diabetic patients with heart failure and preserved ejection fraction (HF-PEF), and to evaluate the correlations between them.Methods 235 out- and hospitalized patients with type 2 diabetes from Department of Cardiology of Affiliated Fuzhou Second Hospital of Xiamen University were enrolled. They were divided into HF-PEF group (120 cases) and non-HF-PEF (HF-NPEF) group (115 cases) according to the diastolic function results of echocardiography. In the HF-PEF group, according to the TCM differentiation of syndromes, the patients were subdivided into four types: heart Qi and Yin deficiency, Yang deficiency of heart and kidney, Qi deficiency and blood stasis and edema syndrome due to Yang deficiency syndromes. The HbA1c levels of different TCM syndromes in HF-PEF and HF-NPEF groups were determined by high performance liquid chromatography. The patients of HF-PEF were further divided into two groups according to serum HbA1c levels > 7.0% or ≤ 7.0%, and the relationships between different serum HbA1c levels and different severity of TCM syndrome types of patients with HF-PEF were compared.Results The level of serum HbA1c in HF-PEF group was significantly higher than that in HF-NPEF group in patients with type 2 diabetes [(7.02±0.74)% vs. (6.79±0.91)%,P 0.05], while the HbA1c levels of Qi deficiency and blood stasis and edema syndrome due to Yang deficiency syndromes were significantly higher than those of heart Qi and Yin deficiency and Yang deficiency of heart and kidney types [(7.15±0.70)%, (7.55±0.62)% vs. (6.70±0.66)%, (6.70±0.68)%], and the HbA1c levels of edema syndrome due to Yang Deficiency was obviously higher than that of Qi deficiency and blood stasis (P 7.0%, the incidence rate of Qi deficiency and blood stasis and edema syndrome due to Yang Deficiency types was higher than that of the group of HbA1c ≤ 7.0% [61.97% (44/71) vs. 38.78% (19/49),P 7.0% (r = 0.683,P < 0.05).Conclusion Clinically using serum HbA1c level to assess the prognosis of HF-PEF has obtained consistent results, and the level is positively correlated to the development of TCM syndrome types in young and middle-aged HF-PEF patients with type 2 diabetes.

Cytogenetic and molecular study of a patient with severe oligozoospermia and asthenozoospermia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore genetic etiologies of a patient with severe oligozoospermia and asthenozoospermia.</p><p><b>METHODS</b>G-banded karyotyping and fluorescence in situ hybridization (FISH) were used to characterize the origin and structure of the abnormal chromosome discovered in this patient. Multiplex polymerase chain reaction (PCR) was used to detect microdeletion of azoospermia factor (AZF).</p><p><b>RESULTS</b>G-banding revealed a karyotype of 45,X,der(15) (?::p11.2→ qter)dn for the patient. Dual-color FISH confirmed that SRY gene was present in a segment attached to the short arm of chromosome 15. Sex chromosome mosaicism and numerical abnormality therefore were both present. Dual-color FISH revealed karyotype of nuc ish(DXZ1× 1, SRY× 1)[390/400]/(DXZ1× 2, SRY× 1) [10/400]. Four-color FISH showed that the abnormal chromosome 15 has derived from a pseudodicentric (Y;15) translocation, and that the breakpoint on Y chromosome was located at Yq12. G-banding and FISH results confirmed that the karyotype was 45,X,der(15)(?::p11.2→ qter)dn.ish psu dic(15;Y)(p11.2;q12)(D15Z1+ , SNRPN+ , PML+ ; SRY+ , DYZ3+ , DYZ1+ ). Microdeletion of AZFc combined with sY254 deletion was detected by multiplex PCR.</p><p><b>CONCLUSION</b>Cytogenetic and molecular genetic analysis of the patient has indicated meiotic disturbances with spermatogenetic arrest resulting from a pseudodicentric chromosome derived from Y;15 translocation and spermatogenesis dysfunction resulting from partial deletion of AZFc region.</p>

Determination of 15 Phthalate Esters in Drinking Water by Solid Phase Extraction-Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

A method of solid phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry ( SPE-UPLC/MS/MS) was developed for the determination of 15 phthalate esters. Drinking water samples were concentrated by C18 SPE cartridge. The fifteen phthalate esters were separated on a phenyl column with gradient elution using methanol and water as mobile phases. Multiple reaction monitoring ( MRM) acquisition under positive ion mode was performed. The external matrix standard solutions were used for the quantitative determination. The linear range of Di-n-butyl phthalate was 0. 63-1000 μg/L. The other 14 phthalate esters showed good linearity in the range of 0 . 002-500 μg/L with the correlation coefficients more than 0. 9970. The limits of quantification ( LOQ) were 2. 2-632 ng/L. The spiked recoveries ranged from 81 . 3% to 109%. The relative standard deviations were less than 14%.