Objective:To analyze the genetic variant characteristics of primary immunodeficiency diseases (PID) in families from Henan Province.Methods:This study conducted a retrospective analysis of 19 PID pedigrees referred to the Prenatal Diagnosis Center at Henan Provincial People's Hospital between January 2016 and March 2024. Among the 19 families, 13 underwent prenatal diagnosis at our hospital, while the remaining six received genetic counseling based on third-party genetic testing reports (confirmed by our institution's laboratory). The clinical data from these families were analyzed, and descriptive statistical analysis was applied to the data.Results:Among the 19 PID families, there were seven cases of combined immunodeficiency, three immunodeficiency syndromes, three phagocyte deficiencies, three antibody-dominant immunodeficiencies, and three immunodysregulatory disorders, involving a total of 12 genes ( IL2RG, ADA, RAG2, STAT3, SMARCAL1, ATM, POLA1, CYBB, BTK, RAB27A, LRBA, IL10R). A total of 25 genetic variants were identified, including 11 novel variants not previously documented in the ClinVar and HGMD professional databases. The novel variants comprised: IL2RG gene mutations (Exon5_8del and c.903_904delinsCT leading to p.E302*), ADA gene mutation (c.884A>G resulting in p.D295G), RAG2 gene mutation (c.513dupA causing p.W172Mfs3), POLA1 gene mutation (c.25+5G>C), CYBB gene mutations (c.824G>A/p.G275D and c.472A>T/p.K158), BTK gene mutations (c.522_523insC/p.A175fs and c.142-2A>C), and RAB27A gene mutations (c.121delA/p.T41fs and c.272delA/p.D91fs). Among the 13 families undergoing prenatal diagnosis, genetic testing revealed that 11 fetuses carried wild-type genes, and these families elected to continue their pregnancies. One fetus exhibited identical genetic variants to the proband and received a clinical diagnosis consistent with the genetic disorder, while another fetus demonstrated chromosomal copy number variations. In both of these latter cases, the families opted for pregnancy termination. Conclusion:This study identified 11 unreported variants across seven genes, highlighting the need for further expansion of PID genetic variant databases.

Objective:To analyze the genetic variant characteristics of primary immunodeficiency diseases (PID) in families from Henan Province.Methods:This study conducted a retrospective analysis of 19 PID pedigrees referred to the Prenatal Diagnosis Center at Henan Provincial People's Hospital between January 2016 and March 2024. Among the 19 families, 13 underwent prenatal diagnosis at our hospital, while the remaining six received genetic counseling based on third-party genetic testing reports (confirmed by our institution's laboratory). The clinical data from these families were analyzed, and descriptive statistical analysis was applied to the data.Results:Among the 19 PID families, there were seven cases of combined immunodeficiency, three immunodeficiency syndromes, three phagocyte deficiencies, three antibody-dominant immunodeficiencies, and three immunodysregulatory disorders, involving a total of 12 genes ( IL2RG, ADA, RAG2, STAT3, SMARCAL1, ATM, POLA1, CYBB, BTK, RAB27A, LRBA, IL10R). A total of 25 genetic variants were identified, including 11 novel variants not previously documented in the ClinVar and HGMD professional databases. The novel variants comprised: IL2RG gene mutations (Exon5_8del and c.903_904delinsCT leading to p.E302*), ADA gene mutation (c.884A>G resulting in p.D295G), RAG2 gene mutation (c.513dupA causing p.W172Mfs3), POLA1 gene mutation (c.25+5G>C), CYBB gene mutations (c.824G>A/p.G275D and c.472A>T/p.K158), BTK gene mutations (c.522_523insC/p.A175fs and c.142-2A>C), and RAB27A gene mutations (c.121delA/p.T41fs and c.272delA/p.D91fs). Among the 13 families undergoing prenatal diagnosis, genetic testing revealed that 11 fetuses carried wild-type genes, and these families elected to continue their pregnancies. One fetus exhibited identical genetic variants to the proband and received a clinical diagnosis consistent with the genetic disorder, while another fetus demonstrated chromosomal copy number variations. In both of these latter cases, the families opted for pregnancy termination. Conclusion:This study identified 11 unreported variants across seven genes, highlighting the need for further expansion of PID genetic variant databases.

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 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 provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.

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.

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4). METHODS: Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing. RESULTS: DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic. CONCLUSION The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.
Base Sequence ; Humans ; Mutation ; Paraplegia/genetics* ; Pedigree ; Sequence Analysis, DNA ; Spastic Paraplegia, Hereditary/genetics* ; Spastin/genetics*

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.

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.