中华医学遗传学杂志最新文献

{"title":"[Clinical features and genetic analysis of a child with Progressive familial intrahepatic cholestasis type 5 due to variant of NR1H4 gene].","authors":"Mengjun Dong, Zhiyi Xia, Suli Li, Yanbing Zhao, Fang Zhou","doi":"10.3760/cma.j.cn511374-20250907-00531","DOIUrl":"10.3760/cma.j.cn511374-20250907-00531","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical, genetic, treatment and prognostic characteristics of progressive familial intrahepatic cholestasis type 5 (PFIC5).</p><p><strong>Methods: </strong>A retrospective analysis was carried out on the clinical data of a child diagnosed with PFIC5 at the Children's Hospital Affiliated to Zhengzhou University in June 2022. Peripheral blood samples from the child and his parents were collected, and trio-whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing and subjected to pathogenicity analysis. A literature search was conducted on various databases to identify previous reports on PFIC5-related cases due to variants of NR1H4 gene. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-H-H02).</p><p><strong>Results: </strong>The child, a 3-month-and-4-day-old boy, presented with persistent jaundice onset from the neonatal period, elevated transaminases and bile acids, while his gamma-glutamyl transferase (GGT) remained normal. Genetic testing revealed that he has harbored c.925C>G (p.L309V) and c.1012G>A (p.E338K) compound heterozygous variants of the NR1H4 gene. Neither of the variants were reported previously. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), both variants were classified as likely pathogenic (PM2_Supporting+PP1+PP2+PP3+PP4; PM2_Supporting+PP1+PM5+PP4). Literature search has identified 1 Chinese and 7 English reports on NR1H4 variant-induced PFIC5, totaling 15 cases including the present one, including 7 cases from China. The age of onset has ranged from 1 day to 16 months, with a median age of 1 week. Typical clinical manifestations have included onset of progressive cholestasis from the neonatal period, elevated transaminases and alpha-fetoprotein, normal GGT, accompanied by hepatosplenomegaly and coagulopathy, which could rapidly progress to end-stage liver disease. Genetic testing is the main diagnostic method. Seven children (46.67%) had undergone liver transplantation. During a follow-up of 1 to 8 years, 6 cases had achieved symptom resolution, while 1 case had deceased 1 year after the transplantation. Of the 8 non-transplanted patients (53.33%, 8/15), 1 had an unknown prognosis and 7 had deceased. Survival rates had differed significantly between the transplantation group and non-transplantation group (Fisher's exact test, P = 0.005).</p><p><strong>Conclusion: </strong>The c.925C>G (p.L309V) and c.1012G>A (p.E338K) compound heterozygous variants of the NR1H4 gene probably underlay the pathogenesis of PFIC5 in this child. For children with early-onset, refractory cholestasis and normal GGT, PFIC5 should be suspected, and genetic testing should be performed to facilitate early diagnosis and treatment.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"450-459"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Analysis of a Chinese pedigree affected with Hereditary factor Ⅴ deficiency due to compound heterozygous variants of F5 gene].","authors":"Yujie Feng, Xiaoli Cheng, Jiayun Liu, Lin Zhu","doi":"10.3760/cma.j.cn511374-20250810-00482","DOIUrl":"10.3760/cma.j.cn511374-20250810-00482","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the clinical characteristics and causative variation sites in a pedigree with hereditary coagulation factor Ⅴ (FⅤ) deficiency.</p><p><strong>Methods: </strong>A pedigree with hereditary FⅤ deficiency who visited Xijing Hospital on March 2, 2025, was selected as the study subject. Clinical data of the pedigree were collected using a retrospective analysis method. Venous blood samples were collected from the proband and family members to obtain platelet-poor plasma and genomic DNA. FⅤ activity (FⅤ:C) was measured by coagulation assay, and FⅤ antigen (FⅤ:Ag) was measured by ELISA for all members. Sanger sequencing was used to detect all exons and flanking sequences of the F5 gene in all members to screen for variations. Thrombin generation assay was performed to evaluate the overall coagulation potential of the proband and parents. Multiple online software tools, including ClustalX-2.1-win, PolyPhen-2, PROVEAN, I-Mutant v2.0, SIFT, Mutation Taster, and Swiss-Pdb Viewer, were used to assess the conservation of the variation sites and their impact on protein structure and function. The pathogenicity of the variation sites was evaluated according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for the interpretation of sequence variants. This study was approved by the Medical Ethics Committee of Xijing Hospital (Ethics No.: KY20252367).</p><p><strong>Results: </strong>The proband's FⅤ:C level was only 1.3%, and the FⅤ:Ag level was only 2.4%. The proband was found to carry the c.653T>C (p.Phe218Ser) variant in exon 5 and the c.5660A>T (p.Glu1887Val) variant in exon 18 of the F5 gene. According to the ACMG guidelines, these two variants were classified as \"Pathogenic\" (PS4+PM2_Supporting+PP1+PP3+PP4+PP5) and \"Likely Pathogenic\" (PM1+PM2_Supporting+PM3+PP1+PP2+PP3+PP4), respectively. The proband's father and grandfather carried the p.Phe218Ser variant in heterozygous state, and the mother and maternal grandmother carried the p.Glu1887Val variant in heterozygous state. The paternal grandmother and maternal grandfather were wild-type. Thrombin generation assay showed delayed thrombin generation and reduced thrombin output in the proband and parents, indicating impaired coagulation function. Bioinformatics analysis revealed that Phe218 and Glu1887 are highly conserved. Both the p.Phe218Ser and p.Glu1887Val variants were predicted to be deleterious, potentially disrupting local protein conformation and stability, which may lead to functional defects.</p><p><strong>Conclusion: </strong>The compound heterozygous variants p.Phe218Ser and p.Glu1887Val may cause a significant decrease in FⅤ:C and FⅤ:Ag by disrupting the structure and function of the FⅤ protein.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"349-355"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical characteristics and genetic analysis of three fetuses with Baraitser-Winter cerebrofrontofacial syndrome and Dystonia-deafness syndrome type 1 due to variants of ACTB gene].","authors":"Yuxin Zhang, Chunxiao Han, Lulu Yan, Changshui Chen, Haibo Li","doi":"10.3760/cma.j.cn511374-20250217-00078","DOIUrl":"10.3760/cma.j.cn511374-20250217-00078","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To study the clinical and genetic characteristics of three fetuses with Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) and Dystonia-deafness syndrome type 1 (DDS1) due to variants of the β-actin (ACTB) gene.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Two fetuses with BWCFF (fetuses 1 ~ 2) and one fetus with DDS1 (fetus 3) at the Affiliated Women and Children's Hospital of Ningbo University between July 2024 and September 2024 were enrolled as the study subjects. Amniotic fluid samples were collected from the fetuses, together with peripheral blood samples from the three couples. Chromosomal karyotyping and trio-whole-exome sequencing (trio-WES) were carried out. Candidate variants were verified by Sanger sequencing, and their pathogenicity was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using \"ACTB gene\", \"Baraitser-Winter brain frontal syndrome\" and \"dystonia-deafness syndrome\" as the key words, relevant literature was retrieved from the PubMed Database, Wanfang Data Knowledge Service Platform, and the China National Knowledge Infrastruture (CNKI) database from their inception to 31 December 2024. A comprehensive analysis was conducted on the features of fetuses with BWCFF and DDS1 resulting from ACTB gene variants. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2024-184).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Fetal ultrasound revealed that fetus 1 had polycystic kidney and full-length ureteral dilation on the right side, fetus 2 had ventricular septal defect, and fetus 3 had pulmonary valve stenosis. Chromosomal karyotypes were normal in all cases. Trio-WES results revealed that the three fetuses had all harbored heterozygous missense variants of the ACTB gene, which were de novo in origin. Based on the guidelines from ACMG, the c.547C&gt;T (p.Arg183Trp) carried by fetus 1 was classified as pathogenic (PM2_Supporting+PP2+PS3_Supporting+PS4_Moderate+PP4+PS2). The c.633C&gt;G (p.Asp211Glu) variant carried by fetus 2 was classified as variant of uncertain clinical significance (PM2_Supporting+PS2_Supporting+PP3_Moderate+PP2), and so was the c.848T&gt;C (p.Met283Thr) variant carried by fetus 3 (PM2_Supporting+PS2_Supporting+PP3_Moderate+PP2). By following the pre-set search strategy, 10 relevant articles reporting prenatal phenotypes of fetuses with ACTB variants were retrieved. Except the DDS1 fetus reported in the present study, all of remaining 15 fetuses (including two from this study) were diagnosed with BWCFF. Their common phenotypes included increased nuchal translucency/nuchal fold in 5 (33.3%), craniofacial anomalies (e.g., hypertelorism, microcephaly, cleft lip/palate) in 7 (46.7%), gastrointestinal anomalies in 6 (40.0%), urinary system abnormalites (e.g., hydronephrosis, renal cysts, pelviectasis) in 5 (33.3%), cardiovascular malformations (e.g., ventricular septal thickening, tricuspid regurgitation) in 6 (40.0), abnormal amniotic ","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"379-388"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Susceptibility to seizures and expression of fibroblast growth factor 17 in rats with Cortical dysplasia and its effects on the hippocampal neurons].","authors":"Tiantian Liu, Hengfang Liu, Yanjie Jia","doi":"10.3760/cma.j.cn20250830-00519","DOIUrl":"10.3760/cma.j.cn20250830-00519","url":null,"abstract":"<p><strong>Objective: </strong>To assess the susceptibility to seizures, expression of fibroblast growth factor 17 (Fgf17) in rats with Cortical dysplasia (CD), and its effect on hippocampal neurons.</p><p><strong>Methods: </strong>Pregnant SPF SD rats were intraperitoneally injected with Carmustine on E17 to establish a model of CD in the offspring rats. The offspring were randomly divided into the normal control, epilepsy group, CD group, and CD plus epilepsy group (n = 20 each). At 6 weeks of age, the rats from the epilepsy and CD plus epilepsy group were intraperitoneally injected with lithium chloride and pilocarpine to induce status epilepticus (SE). Quantitative real-time PCR and Western blotting were used to detect the mRNA and protein levels of Fgf17 at 24 hours and 30 days post-SE, respectively. An electrophysiological signal system was used to record the firing rate, amplitude, and seizure duration of the electroencephalogram (EEG) in rats from the 4 groups at 30 days post-SE. According to the concentration of Fgf17 in the culture medium, 12 1-day-old rats were divided into the control group, 500 nmol/L Fgf17 group, and 1 000 nmol/L Fgf17 group (n = 4 each). Immunofluorescence staining was used to observe the morphometry and number of hippocampal neurons in the 3 groups. This study was approved by the Ethics Committee of the Fifth Affiliated Hospital of Zhengzhou University (Ethics No.: KY2023005).</p><p><strong>Results: </strong>Hematoxylin-Eosin (HE) staining indicated CD in rats from the CD group and CD plus epilepsy group. Compared with the epilepsy group, the CD plus epilepsy group exhibited a faster rate of seizure onset, higher EEG amplitudes, and longer seizure at 30 days post-SE (P < 0.05). Both the CD and the CD plus epilepsy groups showed lower mRNA and protein expressions of Fgf17 in the hippocampus at 24 hours and 30 days post-SE compared with the control and epilepsy groups (P < 0.05), with the expression significantly decreased in the CD plus epilepsy group. Both the 500 nmol/L and the 1 000 nmol/L Fgf17 groups showed a greater number of hippocampal neurons compared with the control group (P < 0.05). The number of hippocampal neurons in the 1 000 nmol/L Fgf17 group was significantly greater compared with the 500 nmol/L Fgf17 group (P < 0.05).</p><p><strong>Conclusion: </strong>Rats with CD exhibit decreased Fgf17 expression and increased epileptogenic susceptibility, which may be associated with reduced number of hippocampal neurons.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"336-341"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical and genetic characterization of two Chinese children with Diencephalo-mesencephalic junction dysplasia syndrome type 1 due to compound heterozygous variants of PCDH12 gene].","authors":"Xiaoyan Xuan, Xiaoke Zhao, Hu Guo","doi":"10.3760/cma.j.cn511374-20250710-00420","DOIUrl":"10.3760/cma.j.cn511374-20250710-00420","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the genetic etiology of two pediatric patients presenting with developmental delay and microcephaly.</p><p><strong>Methods: </strong>Two patients diagnosed with developmental delay and microcephaly at the Children's Hospital of Nanjing Medical University in February 2023 and March 2024 were enrolled. Peripheral blood samples were collected from both children and their parents. Genomic DNA was extracted and subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing. Pathogenicity of the identified variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Structural visualization of the variant proteins was performed using PyMOL software. A literature review was conducted to summarize reports on PCDH12 gene variants associated with Diencephalic-mesencephalic junction dysplasia syndrome type 1 (DMJDS1). This study was approved by the Medical Ethics Committee of Children's Hospital of Nanjing Medical University (Ethics No.: 202402022-1).</p><p><strong>Results: </strong>Patient 1 was a 5-year and 9-month-old female with congenital microcephaly, global developmental delay, distinctive facial features, intellectual disability, gait instability, and ataxia. Brain MRI indicated cerebral dysgenesis. WES revealed compound heterozygous PCDH12 variants: paternal c.522_525delGTCT (p.S175Pfs*22) and maternal c.244G>T (p.E82*). Both variants were classified as pathogenic according to ACMG guidelines. Patient 2 was a 7-day-old male. Prenatal ultrasound showed microcephaly, and fetal MRI revealed a thin corpus callosum. Postnatally, he exhibited primary microcephaly, global developmental delay, and brain MRI findings included widened lateral ventricles, thin corpus callosum, and abnormal morphology of the bilateral cerebral peduncles. WES identified compound heterozygous PCDH12 variants: maternal c.522_525delGTCT (p.S175Pfs*22) and paternal c.466delC (p.L156Wfs*42). The c.466delC variant was classified as pathogenic. Based on the clinical phenotypes and genetic findings, both patients were diagnosed with DMJDS1. PyMOL analysis indicated that all three PCDH12 variants result in protein truncation. A review of 12 published articles identified 44 reported DMJDS1 cases (including the 2 cases in this study) associated with 19 distinct PCDH12 variants, of which only one previous case involved compound heterozygosity; all others were homozygous.</p><p><strong>Conclusion: </strong>Compound heterozygous variants in the PCDH12 gene are likely the genetic cause of microcephaly and developmental delay in these two patients. The c.244G>T and c.466delC variants are novel, thereby expanding the mutational spectrum of the PCDH12 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"356-362"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical and genetic analysis of a patient with Alström syndrome presenting with paroxysmal palpitations].","authors":"Yanzhi Liu, Xiaofeng Li, Chi Cai, Xiaohui Ning, Jing Wang, Hongxia Niu, Min Tang","doi":"10.3760/cma.j.cn511374-20250328-00187","DOIUrl":"10.3760/cma.j.cn511374-20250328-00187","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical features and genetic etiology of a patient with Alström syndrome (ALMS) who presented with paroxysmal palpitations.</p><p><strong>Methods: </strong>Clinical data were collected from a 20-year-old female patient who was admitted to Fuwai Hospital, Chinese Academy of Medical Sciences in April 2024. Her medical history was obtained, and physical examination, auxiliary investigations, and laboratory tests were carried out. Peripheral blood samples were collected from the patient and her parents. Whole-exome sequencing (WES) was performed, followed by bioinformatic analysis to identify candidate variants. Pathogenicity assessment was conducted based on the guidelines from American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was subsequently conducted for the patient and her parents to confirm the presence of the variants and determine their parental origin. The study was approved by the Ethics Committee of the institution (Ethics No.: 2026-3045).</p><p><strong>Results: </strong>The patient exhibited multisystem involvement including paroxysmal atrial flutter, retinitis pigmentosa, type 2 diabetes mellitus, and hypothyroidism. Electrophysiological examination confirmed right atrial isthmus-dependent atrial flutter. The patient underwent successful radiofrequency ablation. WES revealed that she has harbored heterozygous c.9472C>T (p.Lys579GlufsTer17) and c.1734dup (p.Gln3158Ter) variants of the ALMS1 gene. Bioinformatic analysis suggested that both variants can result in significant alteration in the protein. Pathogenicity analysis showed that both variants were unrecorded in the population and disease-related databases and have loss-of-function effects. Based on the ACMG guidelines, both variants were classified as likely pathogenic. Sanger sequencing confirmed that the two variants were inherited from different parents, constituting compound heterozygous variants. The possible mechanisms underlying the patient's clinical manifestations and recent advances in ALMS research were also summarized.</p><p><strong>Conclusion: </strong>Compound heterozygous ALMS1 variants c.9472C>T and c.1734dup probably underlay the pathogenesis of ALMS in this patient. Above findings have expanded the genotype-phenotype spectrum of ALMS and facilitated understanding of its genetic basis, pathogenic mechanism, and clinical manifestations, thereby promoting early diagnosis and standardized management.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"363-371"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with Spastic paraplegia type 56 due to variants of CYP2U1 gene].","authors":"Qimeng Liu, Chunxiao Hua, Kairun Li, Zetian Dong, Lijun Tan, Xianjie Ren, Hongya Wang, Xinxin Sun, Ru Feng, Bing Wang","doi":"10.3760/cma.j.cn511374-20250415-00228","DOIUrl":"10.3760/cma.j.cn511374-20250415-00228","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology for a Chinese family affected with Spastic paraplegia type 56 (SPG56).</p><p><strong>Methods: </strong>Clinical data of the proband were collected. Peripheral blood samples were collected from the proband and her parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out.Candidate variants were validated using Sanger sequencing, and prenatal diagnosis was provided upon the couples's subsequent pregnancy. This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Zhengzhou University (Ethics No.: 2023223).</p><p><strong>Results: </strong>WES revealed that the proband has harbored compound heterozygous variants of the CYP2U1 gene, namely c.471del (p.Ile158Serfs*2) and c.1253C>T (p.Pro418Leu). Sanger sequencing confirmed that the variants were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.471del (p.Leu158Serfs*2) variant was classified as pathogenic (PVS1+PM2_Supporting+PM3_Supporting+PP1), whilst the c.1253C>T (p.Pro418Leu) was categorized as variant of uncertain clinical significance (PM2_Supporting+PM3+PP3). Prenatal diagnosis confirmed that the fetus has harbored that same compound heterozygous variants. Following genetic counseling, the couple had opted to terminate the pregnancy.</p><p><strong>Conclusion: </strong>The compound heterozygous variants of the CYP2U1 gene probably underlay the pathogenesis of of SPG56 in this family. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"342-348"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prenatal genetic analyses for a woman with a rare cryptic reciprocal insertional balanced translocation].","authors":"Weiguo Zhang, Meiying Zhou, Mengxue Wu, Xinghong Di, Diefei Zheng, Wenluo Tu, Weiqing Zhang","doi":"10.3760/cma.j.cn511374-20250311-00147","DOIUrl":"10.3760/cma.j.cn511374-20250311-00147","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic characteristics of a rare pedigree with maternal cryptic reciprocal insertional balanced translocation in order to provide genetic counseling and prenatal diagnosis.</p><p><strong>Methods: </strong>A pregnant woman undergoing prenatal diagnosis at Taizhou Hospital on December 19, 2019 and February 7, 2022 and her family members were selected as study subjects. Clinical data of the pedigree were collected. Chromosomal G-banding analysis was performed on the fetus, the couple, and the parents of the pregnant woman. High-throughput genomic copy number variation sequencing (CNV-seq) was also carried out. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K20201009).</p><p><strong>Results: </strong>The pregnant woman was G₅P₂. Her first pregnancy had delivered by Cesarean section at full-term. The infant had died 10 days after due to hydrocephalus. Her second pregnancy had also delivered by Cesarean section at full-term. The infant underwent resection of congenital megacolon at 6 months of age. At 16 he still showed developmental delay, extremely low intelligence, and language impairment. Her third pregnancy had resulted in spontaneous abortion at 8 weeks of gestation. During her fourth pregnancy, amniotic fluid was collected at 19 weeks for prenatal diagnosis. During her fifth pregnancy, ultrasound revealed mild separation of fetal renal collecting systems, and amniotic fluid was collected at 20 weeks for prenatal diagnosis. The woman's first and second pregnancies were managed by other hospitals, and the result of chromosomal testing was not available. No relevant test was performed upon her third pregnancy. During her fourth pregnancy, analysis of amniotic fluid sample showed a fetal karyotype of 46,U,der(13)ins(13;16)(q31.1;q21q21)mat, and CNV-seq analysis revealed an 8.54 Mb deletion at 13q31.1q31.3 and a 2.88 Mb duplication at 16q21q21. During the fifth pregnancy, analysis of amniotic fluid sample revealed a fetal karyotype of 46,U,der(16)ins(16;13)(q21;q22.2q31.3)mat, and CNV-seq analysis had indicated a 7.8 Mb duplication at 13q22.2q31.1, an 8.54 Mb duplication at 13q31.1q31.3, and a 2.88 Mb deletion at 16q21q21. Analysis of maternal blood sample revealed a karyotype of 46,XX,ins(13;16)(q31.1;q21q21),ins(16;13)(q21;q22.2q31.3), suggested that the woman has carried a cryptic reciprocal insertional balanced translocation, for which the CNV-seq result were normal. The karyotypes and CNV-seq results of her husband and parents were all normal.</p><p><strong>Conclusion: </strong>The deletion or duplication of 13q31.1q31.3 and 16q21q21 may be the genetic etiology of the adverse pregnancies. The unbalanced gametes may have all resulted from the cryptic reciprocal insertional balanced translocation carried by the woman.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"394-400"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Combined CNV-seq and STR polymorphism analysis for the genetic diagnosis of 553 cases of spontaneous abortion].","authors":"Hexuan Zhang, Xiaoyi Zhang, Linjie Li, Sishi Tao, Yonggang Song, Xue Yang, Lei Yu","doi":"10.3760/cma.j.cn511374-20251001-00584","DOIUrl":"10.3760/cma.j.cn511374-20251001-00584","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy and clinical value of combining low-depth whole-genome copy number variation sequencing (CNV-seq) with short tandem repeat (STR) polymorphism analysis in the genetic diagnosis of spontaneous abortion.</p><p><strong>Methods: </strong>Products of conception and clinical data were retrospectively collected from 553 patients who underwent abortion surgery at Guiyang Maternal and Child Health Care Hospital between January 2023 and October 2024. All samples were tested by CNV-seq to detect copy number variations (CNVs) ≥ 100 kb and aneuploidies. STR analysis was performed in parallel to identify abnormalities undetectable by CNV-seq alone, such as triploidy and uniparental disomy (UPD). The correlation between the detection rate of chromosomal abnormalities and factors including maternal age, gestational week, conception method, and history of adverse pregnancy was analyzed. This study was approved by the Medial Ethics Committee of the Guiyang Maternal Child Health Care Hospital (Ethics No.: 2025-10).</p><p><strong>Results: </strong>The initial detection rate of chromosomal abnormalities by CNV-seq alone was 52.98% (293/553). After integrating STR results, 23 cases of triploidy and 1 case of UPD were additionally identified, increasing the overall detection rate to 57.32% (317/553). Autosomal aneuploidy was the most common abnormality (48.26%, 153/317), followed by aneuploidy mosaicism (20.82%, 66/317), sex chromosome aneuploidy (10.41%, 33/317), and pathogenic CNVs (10.41%, 33/317). The most frequent numerical abnormalities were trisomy 16 (9.15%), 45,X (7.57%), and triploidy (7.26%). The chromosomal abnormality detection rate was significantly higher in women of advanced maternal age (≥ 35 years) (67.55%, 102/151) than in those < 35 years (53.73%, 215/402), and significantly higher in the early miscarriage group (< 12 weeks) (60.20%, 307/510) than in the late miscarriage group (20.93%, 9/43) (both P < 0.05). No significant differences in chromosomal abnormality rates were found between the assisted reproductive technology (ART) and natural conception groups, or between groups with ≤ 2 or > 2 previous adverse pregnancies (both P > 0.05).</p><p><strong>Conclusion: </strong>The combined application of CNV-seq and STR polymorphism analysis improves the detection rate of genetic causes in spontaneous abortion. Advanced maternal age and early miscarriage are key risk factors for embryonic chromosomal abnormalities, while ART conception and a limited history of previous abortions showed no significant impact in this study. This integrated strategy provides a reliable basis for the precise etiological diagnosis of abortion and subsequent genetic counseling.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"328-335"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Impact of Maternal cell contamination on the accuracy of short tandem repeat-based prenatal paternity testing].","authors":"Guosong Shen, Wenwen Li, Yaqin Zhang, Qiongshan Li, Wenfeng Yang","doi":"10.3760/cma.j.cn511374-20250825-00506","DOIUrl":"10.3760/cma.j.cn511374-20250825-00506","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the influence of varying degrees of maternal cell contamination (MCC) in amniotic fluid samples on the accuracy of short tandem repeat (STR) - based prenatal paternity testing.</p><p><strong>Methods: </strong>A total of 100 cases undergoing prenatal diagnosis were enrolled in the paternity testing study at Huzhou Maternity and Child Health Care Hospital in January 2025 to June 2025. Amniotic fluid samples were collected via ultrasound-guided amniocentesis. Genomic DNA was extracted from amniotic fluid cells and peripheral blood samples of the presumed parents. A multiplex PCR system (STRtyper-21G) was used to amplify 20 autosomal STR loci and one sex-determining marker. Capillary electrophoresis and genotyping were performed using a Sanger sequencer. The incidence and degree of MCC in actual cases were recorded. To assess detection sensitivity, simulated MCC samples were prepared by mixing maternal peripheral blood DNA with fetal DNA at specific ratios to mimic contamination levels of 50.0%, 20.0%, 10.0%, 5.0%, and 2.0%. These samples were analyzed using the same STRtyper-21G system. This study was approved by Medical Ethics Committee of the Huzhou Maternity and Child Health Care Hospital (Ethics No.: 2024-R-005).</p><p><strong>Results: </strong>Among the 100 amniotic fluid samples, MCC was observed in the following proportions: ≥ 20.0% in 1 case (1.0%), 10.0% - 20.0% in 1 case (1.0%), and 5.0% - 10% in 3 cases (3.0%). Simulation experiments demonstrated that the signal intensity of contamination alleles in electrophoretograms corresponded closely to the proportion of maternal DNA introduced. When MCC was below 5.0%, contaminant allele signals were negligible and did not significantly affect the interpretation of major alleles or the calculation of the paternity index.</p><p><strong>Conclusion: </strong>MCC is a relatively common phenomenon in STR profiling of amniotic fluid cells. In prenatal paternity testing, it is essential to rigorously analyze STR electrophoretograms, accurately identify and exclude contamination peaks derived from MCC, and precisely calculate the cumulative paternity index to ensure reliable conclusions.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 5","pages":"321-327"},"PeriodicalIF":0.0,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}