Prospective research have shown that whole exome sequencing (WES) may be considered when a diagnosis cannot be obtained using routine prenatal methods, e. g., chromosomal karyotyping and copy number variation sequencing, for fetuses with significant structural anomalies. WES can increase the diagnostic rate of genetic disorders in such fetuses by 8%~10%. Prenatal WES has been gaining wide acceptance. However, due to the limitations of fetal phenotypic evaluation and complexity of ethical issues in prenatal diagnosis, to justify and standardize the application of prenatal WES and maximize its clinical utility has become an urgent need. In view of this, a consensus has been formed by referring to the latest guidelines, expert consensus and authoritative literature. This consensus has put forward suggestions on the suitable objects of prenatal WES, pre-test consultation, sampling and laboratory testing, results report, post-test consultation, pregnancy outcome follow-up, multidisciplinary consultation of difficult cases, preservation of prenatal WES samples and data information.

Objective:To summarize the diagnosis features of the prenatal genetic diagnosis of fetal renal cystic disease and to explore the clinical feasibility and significance of prenatal genetic diagnosis of congenital cystic nephrosis.Methods:A total of 25 fetuses with congenital renal cystic disease were examined via invasive prenatal diagnosis in Henan Provincial People's Hospital from June 2017 to September 2019. Amniotic fluid samples were extracted by amniocentesis. Chromosomal microarray analysis (CMA) were performed in 17 cases. In addition to CMA, the other 8 cases were analyzed by G-band karyotype. Whole exome sequencing (WES) was performed in 6 cases which got normal results by CMA and karyotype, and highly suspected as hereditary disease.Results:Of the 25 fetuses assessed, 4 cases (16.0%) pathogenic copy number variation (pCNV) were found, including 2 cases of 17q12 deletion, 1 case of 10p15.1p14 deletion and 1 case of 4q21.28q22.1 deletion(including PKD2 gene). There were 8 cases without chromosome abnormality by karyotype analysis. Six clinical WES analysis found NPHS1 gene c.1440+1 G>A and c.925G > T mutations were related to Finnish type congenital nephrotic syndrome in 1 case, PKD1 gene c.6878C>T mutation was related to autosomal dominant polycystic kidney disease (ADPKD) in 1 case, and there was no definitive mutation in 4 cases. Conclusions:CMA and next generation sequencing are powerful tools for accurate diagnosis, treatment and genetic counseling of fetal congenital renal cystic diseases. For congenital cystic nephropathy, genetic detection is helpful to clarify the etiology, and provide more exactly informations for prognosis evaluation, treatment and family genetic counseling.

OBJECTIVETo assess the association of polymorphisms of human leukocyte antigen DRB1 gene (HLA-DRB1) with susceptibility to unexplained recurrent spontaneous abortion (URSA).

METHODSThe HLA-DRB1 gene was typed with polymerase chain reaction-specific sequence primers (PCR-SSP) method in 200 couples with URSA and 200 couples with a normal pregnancy history.

RESULTSThe frequencies of DRB1*09 and DRB1*13 alleles were significantly greater in the URSA group compared with the control group (14.50% vs. 9.50%, and 7.00% vs. 4.38%, both P<0.05), whilst the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (7.13% vs. 10.75%, and 8.63% vs. 14.38%, both P<0.05). For females from the URSA group, the frequency of DRB1*09 allele (14.00%) was significantly higher compared with the controls (9.25%) (P=0.036), whilst the frequency of DRB1*12(8.50%) allele was significantly lower (14.00%) (P=0.014). For males in the URSA group, the frequencies of DRB1*09 and DRB1*13 alleles were significantly higher than those of the controls (15.00% vs. 9.75%, and 9.25% vs. 4.00%, both P<0.05), whilst the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (5.75% vs. 12.25%, and 8.75% vs. 14.75%, P<0.05).

CONCLUSIONThe DRB1*09 and DRB1*13 alleles may contribute to the susceptibility of URSA, while DRB1*04 and DRB1*12 alleles may confer a protective effect factors. For females, however, no significant association of DRB1*13 and DRB1*04 alleles with URSA was found.

Abortion, Spontaneous ; ethnology ; genetics ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; HLA-DRB1 Chains ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Pregnancy ; Young Adult

Objective To investigate the prognostic effects and failure patterns of different clinical target volumes of IMRT in definitive chemoradiotherapy for cervical and upper-thoracic esophageal cancer,in order to provide a reference for radiotherapy target area delineation.Methods A retrospective analysis was performed on the clinical data of 132 patients with cervical and upper-thoracic esophageal cancer who received definitive IMRT and concurrent chemotherapy in our hospital from 2010 to 2014.Seventy-one patients received elective nodal irradiation (ENI) and the other 61 patients received involvedfield irradiation (IFI).The Kaplan-Meier method was used to calculate local control (LC),progressionfree survival (PFS) and overall survival (OS) rates.The significant difference was evaluated by the logrank test.The prognostic factors were determined by Cox univariate and multivariate analyses.Results The last follow-up time was December 2017,the median follow-up time was 59.5 (14.2-95.8) months.Follow-up rate was 99.2％.For the ENI and IFI groups,the 1-,3-,5-year LC were 77.5％,58.8％,48.8％ vs.64.3％,29.1％,26.2％ (x2=9.68,P=0.002),PFS were 68.6％,37.7％,25.9％ vs.47.5％,17.2％,3.6％ (x2=11.39,P=0.001),OS were 81.7％,53.9％,31.3％ vs.70.5％,31.9％,16.3％ (x2=7.70,P =0.006),respectively.In multivariate analysis,T stage,N stage,and RT field were independent factors for LC,PFS and OS(P＜0.05).The total failure rates,local-regional recurrent rate in ENI group were lower than those in IFI group (x2 =13.23,5.24,P＜0.05).No significant differences were found in acute radiation esophagitis,pneumonitis and myelosuppression (Grades ≥ 3) between the two groups(P＞0.05).Conclusions Compared with IFI,ENI can significantly reduce local-regional recurrence and distant metastasis and improve the long-term survival for cervical and upper-thoracic esophageal cancer patients who received definitive chemoradiotherapy.

OBJECTIVETo explore the value of HLA-DRB1 gene in predicting the outcome of unexplained recurrent spontaneous abortion (URSA) treated with paternal lymphocyte alloimmunization therapy (PLAT) in Henan Hans.

METHODSThree hundred URSA patients were recruited. Following PLAT treatment, they were divided into two groups according to the outcome of pregnancy. Polymerase chain reaction sequence specific primer (PCR-SSP) were conducted to analyze the HLA-DRB1 gene.

RESULTSFor those who have received PLAT treatment, the frequency of HLA-DRB1*11 was significantly lower in successfully treated cases than those with abortion (0.052 vs. 0.110, P < 0.05, OR=0448), whilst the frequency of HLA-DRB1*15 was significantly greater in the former (0.207 vs. 0.100, P < 0.05, OR=2.352).

CONCLUSIONFor patients who have received PLAT treatment, those with HLA-DRB1*15 are more likely to conceive that those with HLA-DRB1*11.

Abortion, Spontaneous ; ethnology ; genetics ; immunology ; therapy ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; Female ; Genetic Predisposition to Disease ; ethnology ; HLA-DRB1 Chains ; genetics ; Humans ; Immunotherapy ; Isoantigens ; immunology ; Lymphocytes ; immunology ; Male ; Pregnancy ; Treatment Outcome

OBJECTIVE To detect potential mutations of the EXT1 and EXT2 genes in a pedigree affected with hereditary multiple exostosis (HME). METHODS For a four-generation family with 7 affected individuals from 17 family members,genomic DNA was extracted from peripheral venous blood samples. All exons of the EXT1 and EXT2 genes were screened for potential mutation by PCR and Sanger sequencing. RESULTS A novel heterozygous frameshift mutation c.1202delT (p.I401Tfs*2)was found in exon 4 of the EXT1 gene in the proband and the other 6 affected individuals. The same mutation was not detected among the healthy members from the family. The mutation has given rise a truncated EXT1 protein with loss of 345 amino acids. CONCLUSION A novel frameshift mutation of the EXT1 gene has been identified in a pedigree affected with HME, which has enriched the mutational spectrum of the EXT1 gene and may facilitate genetic counseling and prenatal diagnosis for the family.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics* ; China ; Female ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Female ; Fetus ; Finland ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Nephrotic Syndrome ; congenital ; diagnosis ; Pregnancy ; Prenatal Diagnosis

This paper reported a rare case of hypercalcemic crisis caused by a parathyroid adenoma with hemorrhage and cystic degeneration. Preoperative imaging examination of the patient was unable to determine the histological origin of the cervical cystic lesion. Despite aggressive medical treatment and hemodialysis, hypercalcemic crisis could not be relieved. Therefore, surgical exploration and excision of the cervical lesion were performed, and final diagnosis of parathyroid adenoma with hemorrhage and cystic degeneration was confirmed by pathology. Blood calcium level and renal function returned to normal after the surgery.

Objective:To explore the therapeutic efficacy and safety of elective nodal irradiation (ENI) and involved field irradiation (IFI) in intensity-modulated radiotherapy for esophageal cancer, screen the patients suitable to undergo ENI radiotherapy and provide evidences for individual treatment of esophageal cancer.Methods:A retrospective analysis was performed on the clinical data of 924 patients with esophageal cancer who received definitive intensity-modulated radiotherapy in our hospital from January 2006 to December 2015. Among them, 272 patients received ENI and the other 652 patients received IFI. The clinicopathologic characteristics of 272 cases in ENI group and 652 cases in IFI group, who were recruited according to the balance of propensity score matching method, were compared. The Kaplan-Meier method was used to calculate 1-year, 3-years and 5-years local-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS) rates. The univariate and multivariate analysis of prognostic factors were also determined by Cox proportional hazard model and Long-rank test.Results:The clinicopathologic characteristics of these two group were not significantly different ( P>0.05). The median follow-up time was 85.9 months and the follow-up rate was 95.9%. The 1-year, 3-years, 5-years PFS rates of the ENI groups were 65.3%, 31.7%, 18.4%, respectively, higher than 54.0%, 20.9%, 12.7% of the IFI group ( P=0.001). The 1-year, 3-years, 5-years OS rates of the ENI groups were 79.0%, 43.7%, 24.9%, respectively, higher than 75.0%, 31.8%, 17.2% of the IFI group ( P=0.003). In multivariate analysis, the sex, tumor volume, N stage and radiation field were independent factors for PFS and OS ( P<0.05). Subgroup analysis showed that patients with male, age≤66 year, cervical and upper-thoracic location, tumor length≤6 cm, T1-2 stage, N0-1 stage, Ⅰ-Ⅱ stage, tumor volume≤50 cm 3, dosage>60 Gy and≤2 cycles of chemotherapy in the ENI group had a better survival rate than those in the IFI group ( P<0.05). The total failure rate, local-regional failure rate in ENI group were significantly lower than those of IFI group ( P=0.001, P=0.004). The incidence of bone marrow depression≥ grade 2 and 3 in ENI group was higher than that of the IFI group ( P<0.05). However, the incidences of radioactive esophagitis≥ grade 3, radioactive pneumonia and late adverse reactions were not significantly different between these two groups ( P>0.05). Conclusion:Compared with IFI, ENI can significantly improve the long-term survival for young, early TN stage and cervical/upper-thoracic esophageal cancer patients underwent chemotherapy.