Application of low-depth whole genome sequencing for copy number variation analysis in children with disorders of sex development / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD).@*METHODS@#Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out.@*RESULTS@#Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25].@*CONCLUSION@#CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.

Construction and operation of hospital radiation protection management information system / 中华医院管理杂志

The construction and operation of the hospital-wide radiation protection management information system is of great significance for improving the efficiency and quality of radiation protection management. A hospital has built a hospital-wide radiation protection management system, which consisted of four modules: radiation staff management module, protection items management module, site and equipment management module, and self-inspection module. The system adopted B/S mode, carried the lightweight J2EE framework-SpringBoot framework, and used mybatis, which was flexible and practical, as the persistence layer of the system, to store the data completely in the SQLServer database.Java language was used as the system development language, and the front and back-end separation architecture was used. Each of the four modules implemented the management responsibility departments and responsible personnel to carry out the all-round management of radiation protection, and realized the integrated, information-based and standardized management of radiation protection management in the hospital.

Quantitative perfusion histogram parameters of dynamic contrast-enhanced MRI to identify different pathological types of uterine leiomyoma / 浙江大学学报·医学版

:To explore the value of quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI） in pathological classification of uterine leiomyoma and its correlation with Ki-67 protein expression. Thirty five patients with uterine leiomyoma confirmed by operation and pathology at Shaoxing People's Hospital from October 2015 to September 2017 were analyzed retrospectively，including 15 cases of ordinary type，8 cases of cellular type and 12 cases of degenerative type. All patients were examined by pelvic DCE-MRI before operation，and the histogram parameters （median，mean，skewness，kurtosis，energy，entropy） of various quantitative perfusion parameters，including volume transport constant （K），rate constant （K），extravascular extracellular space distribute volume per unit tissue volume （V），blood plasma volume per unit volume of tissue （V） were calculated，and the efficacy of different parameters in pathological classification of uterine leiomyoma was evaluated by ROC curve. The expression of Ki-67 protein in uterine leiomyoma was detected by immunohistochemical method，and the correlation between histogram parameters and Ki-67 protein expression was analyzed by Pearson and Spearman correlation analysis. The median and mean values of K，K，V and V in the cellular group were higher than those in the degenerative group and the ordinary group（<0.05 or <0.01），while the skewness of V，the skewness and kurtosis of K in the cellular group were lower than those in the ordinary group （all <0.05）. The entropy of K in the cellular group was higher than that in the degenerative group and the ordinary group （all < 0.05）. The entropy of V in the cellular group was higher than that in the ordinary group （<0.01）. The median，mean，skewness of K，median and mean of K，median and mean of V，median，mean，energy and entropy of V were correlated with Ki-67 expression（all <0.05）. The results of ROC curve analysis showed that the median threshold of K was 0.994/min，the sensitivity and specificity for the diagnosis of cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.949. When the mean threshold of K was 1.170/min，the sensitivity and specificity for diagnosing cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.958. The area under the ROC curve of K （entropy），K （median，mean），V （median，mean，entropy） in the diagnosis of cellular uterine leiomyoma were 0.755-0.907. :DCE-MRI quantitative perfusion histogram parameters have high diagnostic value in differentiating pathological types of uterine leiomyoma，especially for cellular uterine leiomyoma.

Genetic screening and prenatal diagnosis in high-risk families with tuberous sclerosis complex syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis.@*METHODS@#NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands.@*RESULTS@#Twenty-seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2 genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected.@*CONCLUSION@#Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.

Assisting Scalable Diagnosis Automatically via CT Images in the Combat against COVID-19

Introductory paragraphThe pandemic of coronavirus Disease 2019 (COVID-19) caused enormous loss of life globally. 1-3 Case identification is critical. The reference method is using real-time reverse transcription PCR (rRT-PCR) assays, with limitations that may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that application of deep learning (DL) to the 3D CT images could help identify COVID-19 infections. Using the data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 patients. COVIDNet achieved an accuracy rate of 94.3% and an area under the curve (AUC) of 0.98. Application of DL to CT images may improve both the efficiency and capacity of case detection and long-term surveillance.

Effect of tantalum coating on adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells / 中华创伤骨科杂志

Objective:To investigate the effects of tantalum coating on adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods:In this study, BMSCs were extracted from 6 6-week-old rats and cultured in vitro to the third generation. Tantalum coating was manufactured on Ti6Al4V by chemical vapor deposition. The cells were identified by flow cytometry before they were induced with different mediums for osteogenesis, chondrogenesis and adipogenesis. The adhesion, proliferation and osteogenic differentiation of BMSCs were detected with fluorescence staining, Cell Counting Kit-8 (CCK8) assay and Q-PCR, respectively. Recorded and compared were the adhesion rate, proliferation rate, and expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), osteonectin (OSN) and osteopontin (OPN) of BMSCs on the surface of titanium alloy round plates (the Ti6Al4V group) and of tantalum coating round plates (the Ta group). Results:The flow cytometry revealed CD44 (94.55%), CD90 (95.01%) and CD34 (0.06%). Alkaline phosphatase (ALP) staining was positive after osteogenic induction for 14 days; Alizarin red staining showed calcified nodules after osteogenic induction for 21 days; oil red O staining was positive after adipogenic induction for 21 days; alcian blue staining found chondrogenic ability after chondrogenic induction for 21 days. Laser confocal microscopy showed that the BMSCs grew in patches aggregated and closely linked on the surface of titanium alloy round plates (in the Ti6Al4V group) and of tantalum coating round plates (in the Ta group). More BMSCs adhered on the tantalum coating plates than on the titanium alloy plates and exhibited better ductility. The proliferation rates of BMSCs on tantalum coating were significantly faster than those on titanium alloy after 1, 3, 5 and 7 days of co-culture in vitro ( P<0.05).Q-PCR showed that tantalum coating promoted the expression of OSN and OPN after 7 days of culture significantly higher than titanium alloy did ( P<0.05).After 21 days of co-culture in vitro, tantalum coating enhanced the expression of OSX, RUNX2, OSN and OPN significantly higher than titanium alloy did ( P<0.05). Conclusion:Compared to titanium alloy which is used for conventional orthopedic implants, tantalum coating can observably promote adhesion, proliferation and osteogenic differentiation of BMSCs.

Value of myocardial scar in predicting malignant ventricular arrhythmia in patients with chronic myocardial infarction / 浙江大学学报·医学版

OBJECTIVE@#To assess the predictive value of myocardial scar mass in malignant ventricular arrhythmia (MVA) after myocardial infarction.@*METHODS@#Thirty myocardial infarction patients with complete electrophysiology and cardiac MRI data admitted from January 2012 to August 2017 were enrolled in the study. According to the results of intracavitary electrophysiological study, MVA developed in 16 patients (MVA group) and not developed in 14 patients (non-MVA group). The qualitative and quantitative analysis of left ventricular ejection fraction (LVFE) and scar mass was performed with CV post-processing software and predictive value of myocardial scar and LVEF for MVA after myocardial infarction was analyzed using ROC curves.@*RESULTS@#LVEF in MVA group was significantly lower than that in non-MVA group, and scar mass in MVA group was significantly higher than that in non-MVA group (all <0.05). Regression analysis showed that LVEF (=1.580) and scar mass (=6.270) were risk factors for MVA after myocardial infarction. For predicting MVA, the area under ROC curve () of LVEF was 0.696 with a sensitivity of 0.786 and the specificity of 0.685; the of the scar mass was 0.839 with a sensitivity was 0.618 and the specificity of 0.929; the of LVEF combined with scar mass was 0.848 with a sensitivity of 0.688 and specificity of 0.857.@*CONCLUSIONS@#Myocardial scar assessed by late gadolinium enhancement MRI is more effective than LVEF in predicting MVA after myocardial infarction.

Prenatal diagnosis for two families affected with cleidocranial dysplasia due to novel RUNX2 variants / 中华医学遗传学杂志

Objective@#To analyze variants of RUNX2 gene in two pedigrees affected with cleidocranial dysplasia and provide prenatal diagnosis for them.@*Methods@#For the two probands, the coding sequences of the RUNX2 gene were analyzed with PCR and bidirectional Sanger sequencing. To verify the results, peripheral blood samples were collected from their parents and 100 healthy controls. For family 1, umbilical cord blood was also collected for prenatal genetic diagnosis.@*Results@#In family 1, the proband and the fetus both carried a heterozygous c. 578G>C (p.Arg193Pro) mutation. For family 2, the proband was found to carry a heterozygous c. 909C>A (p.Tyr303X) mutation. The same mutations were not found among their parents and 100 healthy controls. Neither mutation was reported previously.@*Conclusion@#Variants of the RUNX2 gene probably underlie the cleidocranial dysplasia in both pedigrees. The results enabled prenatal diagnosis for the affected family.

Clinical study of modified prone position in reducing the incidence of pressure injury in patients with prone position ventilation / 中国实用护理杂志

Objective@#To study the effect of using modified prone position to reduce the occurrence of pressure injury in patients with prone position ventilation.@*Method@#Totally 64 patients with prone position ventilation from February 2014 to February 2018 were selected in the Department of Intensive Care of the Drum Tower Hospital, Medical College of Nanjing University. Twenty-six patients with prone position ventilation From February 2014 to February 2016 were selected as the control group. The patients in the control group were in a horizontal prone position, with soft pillows under both sides of the shoulders and hips along the longitudinal axis of the patient (vertical axis), and gel pads under chests; Thirty-eight patients with prone position ventilation from March 2016 to February 2018 were selected as the experimental group. The patients in the experimental group were positioned on turnover sliding cloth, soft pillows were placed under the sliding cloth, on one side along the vertical axis (vertical axis) of the patients, and the soft pillows were repositioned to other side of the patients every 4 hours, i.e. the patients were turned over in the prone position. The incidence of pressure injury, the number of occurrences (each site marked as 1) and the incidence of other related complications were compared between the two groups.@*Results@#The incidence of pressure injury in the experimental group was 10.53% (4/38) and 46.15% (12/26), in the control group. The median and quartile of the number of pressure injuries in the experimental group were 0 (0,0), and 0 (0,2) in the control group. Statistical analysis was performed using the rank sum test. The difference was statistically significant (F=10.287,11.469, P<0.05). Among other related complications, the unplanned extubation rate was 0.38%(1/26) in the control group and 0 in the experimental group. No aspiration occurred in both groups.@*Conclusions@#The use of a modified prone position can reduce the incidence of pressure injuries and reduce the incidence of other related complications, by reducing the duration of skin pressure and decreasing the friction and shear force. It is worthy of popularization and application in clinical practice.

ThevalueofDCEGMRIparametersofReferenceRegionandExtendedToftsmodel indifferentiatehyperGcellularuterineleiomyoma / 实用放射学杂志

Objective ToanalyzethevalueoftheDCE-MRIparametersofReferenceRegionandExtendedToftsmodleinthedifferential diagnosisofhyper-cellularuterineleiomyoma.Methods 59patientswithuterineleiomyomaconfirmedbysurgeryandpathologywere enrolledinthestudyfromSeptember2015toSeptember2016,including28casesofclassicalleiomyoma,12casesofcellularleiomyoma and19casesofdegenerativeleiomyoma.AllpatientsunderwentDCE-MRIbeforesurgery.Thequantitativeperfusionparameters (transferconstant(Ktrans),extravascularextracellularspacevolumeratio(Ve),effluxrateconstant(Kep),andbloodplasmavolume ratio(Vp)weremeasuredviaReferenceRegionmodel(RR model)andExtendedToftsmodel(ET model)respectively.ROCcurve wasusedtoevaluatetheefficiencyofthequantitativeperfusionparametersindifferentialdiagnosisofhyper-cellularuterineleiomyoma. Pearsoncorrelationanalysiswasalsoappliedtoobservethecorrelationsamongallequivalentparameters.Results KtransandKepinRR modelandKtrans,Kep,VeandVpinET modelshowedstatisticalsignificancesamongthreetypesofuterineleiomyoma (P＜0.05), meanwhile,theAUCsofKtrans,KepandVpderivedfrom RR modelandKtrans,Kep,VeandVpcalculatedbyET modelindiagnosisof cellularuterineleiomyomawere0.835,0.752,0.706,0.956,0.871,0.656and0.754.TheKtransintheRR modelwascorrelatedwith KtransintheET model(r＝0.600,P＜0.001),KepintheET modelwaspositivecorrelatedwithKepandVpinRR model(r＝0.275, P＝0.035;r＝0.376,P＝0.003).Conclusion Thevalueof Ktrans ,Kep and Vp in RR and Ktrans ,Kep ,Ve and Vp in ET modelcan be useful inthedifferentiationofhyper-cellularleiomyoma,especiallythevaluesofKtransandKepinET modelhavehigherdiagnosticefficacy thanthoseinRR model.

Prenatal diagnosis for two families affected with cleidocranial dysplasia due to novel RUNX2 variants / 中华医学遗传学杂志

OBJECTIVE@#To analyze variants of RUNX2 gene in two pedigrees affected with cleidocranial dysplasia and provide prenatal diagnosis for them.@*METHODS@#For the two probands, the coding sequences of the RUNX2 gene were analyzed with PCR and bidirectional Sanger sequencing. To verify the results, peripheral blood samples were collected from their parents and 100 healthy controls. For family 1, umbilical cord blood was also collected for prenatal genetic diagnosis.@*RESULTS@#In family 1, the proband and the fetus both carried a heterozygous c.578G>C (p.Arg193Pro) mutation. For family 2, the proband was found to carry a heterozygous c.909C>A (p.Tyr303X) mutation. The same mutations were not found among their parents and 100 healthy controls. Neither mutation was reported previously.@*CONCLUSION@#Variants of the RUNX2 gene probably underlie the cleidocranial dysplasia in both pedigrees. The results enabled prenatal diagnosis for the affected family.

Analysis of ADAR gene mutations in two pedigrees affected with dyschromatosis symmetrica hereditaria / 中华医学遗传学杂志

OBJECTIVE@#To detect mutations of ADAR gene in two pedigrees affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#Potential mutations of the ADAR gene were analyzed by Sanger sequencing of the probands from both pedigrees. Suspected mutations were validated by Sanger sequencing of other patients from both pedigrees as well as unrelated healthy individuals.@*RESULTS@#A heterozygous nonsense mutation c.1325C>G (p.Ser442Ter) and a novel nonsense mutation c.1498C>T (p.Gln500Ter) were respectively identified in the ADAR gene among all patients from the two pedigrees but not among 200 healthy individuals.@*CONCLUSION@#Mutations of the ADAR gene probably underlie the DSH in the two pedigrees. Above findings have enriched the spectrum of ADAR gene mutation.

Correlation between quantitative perfusion histogram parameters of Dynamic Contrast-Enhanced MRI and tumor tis-sue microvessel density in patients with lung cancer / 中华胸心血管外科杂志

Objective To investigate the correlation between quantitative perfusion histogram parameters of DCE-MRI and tumor tissue microvessel density(MVD) in patients with lung cancer.Methods 30 patients with lung cancer confirmed by pathology who underwent preoperative DCE-MRI were enrolled in this retrospective study .Quantitative perfusion histogram pa-rameters( including median, mean, skewness, kurtosis, energy, entropy) were measured for each patient using Exchange mo-dle.Using the Immunohistochemical method to detect the expression of CD34 in tumor tissue, and counting the number of mi-crovessels under microscope.SPSS 19.0 was used to carry out statistical analysis.The correlation between MVD and quantita-tive perfusion histogram parameters of DCE-MRI measured by exchange model was evaluated by Pearson linear correlation anal-ysis.Results There was no significant difference in MVD and each quantitative perfusion histogram parameters between the three different pathological groups of lung cancer(P >0.05).Ktrans perfusion histogram parameters(mean, 25％, 50％, 50％, 75％, 90％, 95％), Kep perfusion histogram parameters(entropy, 10％, 25％, 50％, 75％, 90％), Fp perfusion histogram parameters( mean, 25％, 50％, 75％, 90％, 95％) and Vp perfusion histograms parameters ( entropy, 75％, 90％, 95％ ) were positively correlated with MVD(P<0.05).Ktrans perfusion histogram parameters(energy) and Vp perfu-sion histogram parameters(skewness, kurtosis, energy) were negatively correlated with MVD(P<0.05).There was no signifi-cant correlation between Ve perfusion histogram parameters and MVD(P>0.05).Conclusion There was a certain correla-tion between the perfusion histogram parameters of DCE-MRI and MVD,suggesting that the quantitative perfusion histogram of DCE-MRI in lung cancer can reflect the MVD value of cancer tissue .

Clinical study of modified prone position in reducing the incidence of pressure injury in patients with prone position ventilation / 中国实用护理杂志

Objective To study the effect of using modified prone position to reduce the occurrence of pressure injury in patients with prone position ventilation. Method Totally 64 patients with prone position ventilation from February 2014 to February 2018 were selected in the Department of Intensive Care of the Drum Tower Hospital, Medical College of Nanjing University. Twenty-six patients with prone position ventilation From February 2014 to February 2016 were selected as the control group. The patients in the control group were in a horizontal prone position, with soft pillows under both sides of the shoulders and hips along the longitudinal axis of the patient (vertical axis), and gel pads under chests;Thirty-eight patients with prone position ventilation from March 2016 to February 2018 were selected as the experimental group. The patients in the experimental group were positioned on turnover sliding cloth, soft pillows were placed under the sliding cloth, on one side along the vertical axis (vertical axis) of the patients, and the soft pillows were repositioned to other side of the patients every 4 hours, i.e. the patients were turned over in the prone position. The incidence of pressure injury, the number of occurrences (each site marked as 1) and the incidence of other related complications were compared between the two groups. Results The incidence of pressure injury in the experimental group was 10.53% (4/38) and 46.15% (12/26), in the control group. The median and quartile of the number of pressure injuries in the experimental group were 0 (0,0), and 0 (0,2) in the control group. Statistical analysis was performed using the rank sum test. The difference was statistically significant (F=10.287,11.469, P<0.05). Among other related complications, the unplanned extubation rate was 0.38% (1/26) in the control group and 0 in the experimental group. No aspiration occurred in both groups. Conclusions The use of a modified prone position can reduce the incidence of pressure injuries and reduce the incidence of other related complications, by reducing the duration of skin pressure and decreasing the friction and shear force. It is worthy of popularization and application in clinical practice.

Auditory characteristics of noise-exposed memberscrossing age-related groups.

OBJECTIVE: To report audiological characteristics in a group of noise-exposed crew members on board ships. METHODS AND MATERIALS: Clinical and audiological measurements including pure-tone thresholds, acoustic immittance results and tinnitus questionnaires were collected from both the ship crew members (study subjects) and their land based colleagues (controls). RESULTS: 1) Noise exposed crew members showed not only high frequency, but also low frequency hearing loss; 2) Hearing impairment increased with age, with 65.5% of crew members younger than 50 years showing normal hearing while only 14.9% of those older than 50 years had normal hearing; 3) hearing loss gradually increased with the extension of on board career time; and 4) Most study subjects reported high pitch tinnitus, significantly more than the control group although not significantly different among different age groups. CONCLUSION: Noise induced hearing impairment from working on board ships shows specific frequency and age characteristics. Understanding these characteristics is important for advancing relevant studies and for effective prevention of noise-induced hearing loss in ship crew members.

Quantitative perfusion histogram parameters of dynamic contrast-enhanced MRI to identify cellular leiomyoma / 中华放射学杂志

Objective To evaluate the value of histogram parameters of dynamic contrast-enhanced MRI (DCE-MRI) in the diagnosis of cellular leiomyoma. Methods Seventy one patients with leiomyomas confirmed by pathology who underwent preoperative DCE-MRI were enrolled in this retrospective study. Quantitative perfusion histogram parameters (including median, mean, skewness, kurtosis, energy, entropy) were measured for each patient. Leiomyoma was divided into degeneration, ordinary and cellular types according to pathology. One-way analysis of variance and Least significant difference were used to compare the differences among the parameters of the three groups which were normal distribution and equal variances, while Kruskal-Walls test and Mann-Whitney U test were used to compare the parameters that did not conform to normal distribution or variance. ROC curves were drawn to evaluate the diagnostic efficiency of different parameters. Results Among the three groups,the values of Ktrans(median, mean, kurtosis, energy, entropy), Kep(median, mean, skewness, kurtosis, entropy), Ve(median, mean, skewness, kurtosis) and Vp(median, mean, skewness, kurtosis, energy, entropy) had statistical difference (all P<0.05). The values of Ktrans, Kep, Vp (median, mean) and Ktrans (entropy) of the cellular group were higher than those of the degeneration and ordinary groups. While the values of Ktrans (kurtosis, energy) and Kep (skewness) of the cellular group were lower than the other two groups;then the value of Kep (kurtosis) of the cellular group was lower than the ordinary group and the value of Kep (entropy) of the cellular group was higher than the ordinary group;and the values of Ve (median, mean, kurtosis) and Vp (entropy) of the cellular group were higher than those of the ordinary group. The values of Ve (skewness) and Vp (skewness, kurtosis and energy) of the cellular group were lower than those of degeneration group. ROC curves found that when Ktrans(median)was 0.994/min, its sensitivity was 100.0％, the specificity was 73.8％, and the area under ROC was 0.905;when Ktrans(mean) was 1.170/min, its sensitivity was 90.0％, the specificity was 85.2％, the area under ROC was 0.921. And the areas under ROC of Ktrans (kurtosis, energy, entropy), Kep (median, mean, skewness, kurtosis, entropy), Ve (median, mean, skewness), Vp (median, mean, skewness) were also high (ranging from 0.711 to 0.872). Conclusion Histogram analysis of DCE-MRI quantitative perfusion is applicable for identification of cellular leiomyoma.

Mutation analysis and prenatal diagnosis for a pedigree affected with maple syrup urine disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To carry out mutation analysis for a pedigree affected with maple syrup urine disease (MSUD).</p><p><b>METHODS</b>Clinical data of the proband was collected. Potential mutations of the BCKDHA and BCKDHB genes were analyzed by PCR and Sanger sequencing. Prenatal diagnosis was provided to a high-risk fetus at 12th gestational week through chorionic villus sampling.</p><p><b>RESULTS</b>Two heterozygous mutations c.284G>C (p.Gly95Ala) and c.853C>T (p.Arg285*) of the BCKDHB gene were identified in the proband, which were inherited from his mother and father, respectively. Among these, c.853C>T (p.Arg285*) was known to be pathogenic, while c.284G>C (p.Gly95Ala) was a novel mutation. Prenatal diagnosis showed that the fetus has inherited the c.284G>C (p.Gly95Ala) mutation from its mother but no mutation from its father. After birth, the infant appeared to be healthy.</p><p><b>CONCLUSION</b>The compound heterozygous mutations c.284G>C (p.Gly95Ala) and c.853C>T (p.Arg285*) probably underlie the pathogenesis of MUSD in the proband. Mutation analysis can facilitate prenatal diagnosis and genetic counseling for the affected families.</p>

Characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province / 中华医学遗传学杂志

OBJECTIVE@#To explore the characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province.@*METHODS@#The 13 exons of the PAH gene were subjected to PCR amplification and direct sequencing. Large fragment deletion and duplication of the PAH gene were detected with a multiple ligation-dependent probe amplification (MLPA) assay.@*RESULTS@#In total 195 point variants and 3 large fragment deletions were detected among the 226 alleles, with the detection rates being 86.28% and 1.33%, respectively. Variants of p.Arg243Gln (18.14%), p.Arg111X (6.19%), p.Arg53His (5.31%), EX6-96A>G (5.31%), p.Tyr356X (4.87%) and p.Val399Val (4.42%) were relatively common. Most of the variants were located in exons 7, 11, 3 and 6. Missense variations were most common. Four novel variations were detected, which included c.1016C>A (p.Ser339Tyr), c.1000T>C (p.Cys334Arg), c.1110G>T (p.Glu370Asp), and IVS6+1G>T.@*CONCLUSION@#The PAH gene variations in Henan Province have featured extensive allelic heterogeneity and variety.