中华医学遗传学杂志最新文献

{"title":"[Genetic sequencing and analysis of a patient with ABO blood group Bw28 subtype].","authors":"Siqun Hu, Jinrong Chen, Kaizhao Huang, Suiyong Zhu, Zhengjing Wen, Jiajin Lin","doi":"10.3760/cma.j.cn511374-20250428-00258","DOIUrl":"10.3760/cma.j.cn511374-20250428-00258","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the gene sequence, protein structure, and impact of the variant on glycosyltransferase B (GTB) structural stability in a patient with a ABO*Bw.28 subtype.</p><p><strong>Methods: </strong>A 33-year-old man with mixed hemorrhoids, confirmed as ABO*Bw.28 by genetic sequencing at the Second Affiliated Hospital of Wenzhou Medical University on December 8, 2022 was selected as study subject. ABO phenotyping was performed using tube test, microcolumn gel assay, and absorption-elution test. Genetic testing was conducted by PCR-direct sequencing, with haplotype confirmation by TOPO-TA cloning. Homology modeling was performed using PyMOL, and 100 ns molecular dynamics simulations of wild-type and mutant GTB were conducted using GROMACS to assess root-mean-square deviation (RMSD), radius of gyration (Rg), solventaccessible surface area (SASA), hydrogen bonds, and binding free energy. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-K-289-01).</p><p><strong>Results: </strong>Serological tests revealed characteristics of Bw subtype. ABO gene sequencing identified a c.541T>C variant in exon 7, resulting in p.Trp181Arg substitution. Haplotype analysis confirmed presence of the ABO*Bw.28 allele. Molecular modeling showed that the Trp181Arg substitution largely abolished hydrophobic interactions with the UDP-galactose (UDP-Gal) ligand and reduced the number of active site hydrogen bonds (wildtype: 2 ~ 8; variant: 1 ~ 6). Molecular dynamics simulation suggested increased binding free energy from 11.586 kcal/mol (wild type) to 4.680 kcal/mol (variant), indicating a disrupted local hydrogen bond network and reduced conformational stability and substrate binding affinity.</p><p><strong>Conclusion: </strong>This study has identified a case with a c.541T>C (p.Trp181Arg) ABO variant. The variant may disrupt the hydrophobic interactions and local hydrogen bond network, reducing GTB catalytic domain stability and B antigen expression, thus providing a molecular basis for the Bw.28 subtype.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 7","pages":"541-547"},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319597","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 child with Oculocutaneous albinism due to compound heterozygous variants of OCA2 gene].","authors":"Shuqi Zheng, Xiangyu Zhao, Kai Liu, Hongyan Xu, Wei Gao","doi":"10.3760/cma.j.cn511374-20250830-00518","DOIUrl":"10.3760/cma.j.cn511374-20250830-00518","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology of a child with Oculocutaneous albinism (OCA).</p><p><strong>Methods: </strong>A child diagnosed with OCA at Linyi People's Hospital in December 2020 was selected as study subject. Clinical data were retrospectively analyzed. Whole exome sequencing (WES) was carried out for the child. Based on WES data, potential pathogenic variants and copy number variation (CNV) were screened. Candidate variants were validated by Sanger sequencing and quantitative real-time polymerase chain reaction (qPCR). Bioinformatics tools were employed to predict the structural and functional impacts of the variant. This study was approved by the Medical Ethics Committee of th hospital (Ethics No.: YX200082).</p><p><strong>Results: </strong>WES revealed that the child has harbored compound heterozygous variants of the OCA2 gene, namely c.2323G>A (p.G775Ser) and c.exon3_19del. Sanger sequencing and qPCR confirmed that the variants were inherited from his father and mother, respectively. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the c.2323G>A variant was classified as likely pathogenic (PM1+PM3+PM2_Supporting+PP3+PP4), whilst the c.exon3_19del variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Structural modeling of the truncated protein by SWISS-MODEL software predicted that the c.exon3_19del variant can significantly alter the protein structure and is likely to impair its function.</p><p><strong>Conclusion: </strong>The compound heterozygous variants c.2323G>A (p.G775S) and c.exon3_19del of the OCA2 gene probably underlay the pathogenesis of OCA in this patient. Above finding has enriched the mutational spectrum of the OCA2 gene. CNV analysis based on WES data can serve as a complementary strategy for screening conventional variant types, enabling accurate determination of the origin and size of genomic fragments.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"460-465"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844166","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 of a fetus with renal dysplasia/hypoplasia due to a variant of GREB1L gene and literature review].","authors":"Danning Ma, Shunfei Ma, Xiangyu Liu, Xuan Shang, Fang Yang, Fu Xiong, Yuanling Xiao","doi":"10.3760/cma.j.cn511374-20260116-00027","DOIUrl":"10.3760/cma.j.cn511374-20260116-00027","url":null,"abstract":"<p><strong>Objective: </strong>To carry out clinical and genetic analysis for a fetus with absent kidneys and bladder.</p><p><strong>Methods: </strong>Clinical data of the fetus were collected. Whole exome sequencing (WES) and Sanger sequencing were carried out on fetal tissue and peripheral blood samples from its family members. A RDDC online tool was used to predict the impact of the variant on the GREB1L gene splicing, which was further validated by in vitro minigene assays. Long-range PCR was employed to verify the exonic deletional variant. An I-TASSER server was used to predict the three-dimensional structure of the mutant protein. A systematic search of Chinese and English databases was conducted using \"GREB1L gene\" as the keyword to summarize the clinical phenotypic spectrum associated with GREB1L gene mutations. This study was approved by the Medical Ethics Committee of the Pearl River Hospital of South Medical University (Ethics No.: 2023-KY-016).</p><p><strong>Results: </strong>The fetus was confirmed to have bilateral renal agenesis by autopsy. WES and Sanger sequencing revealed that the fetus, its father and grandfather have all carried a heterozygous c.4369-3_4375del variant of the GREB1L gene (NM_001142966.3), whilst its mother and grandmother did not carry the same variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was rated as \"pathogenic\". As predicted by bioinformatics analysis and confirmed by the minigene assay, this deletional variant may lead to aberrant splicing of exon 26 and result in alteration in the protein's three-dimensional structure. Literature review indicated that GREB1L gene mutations mainly cause renal dysplasia with significant clinical heterogeneity.</p><p><strong>Conclusion: </strong>The heterozygous c.4369-3_4375del variant of the GREB1L gene probably underlay the pathogenesis of renal dysplasia/hypoplasia in this fetus. Discovery of this novel splicing site variant has enriched the mutational spectrum of the GREB1L gene and provided a basis for clinical diagnosis and genetic counseling.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"436-442"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844295","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 four Chinese pedigrees affected with NAA15-related intellectual developmental disorder].","authors":"Xiaoyan Xuan, Jian Tang, Xiaoke Zhao","doi":"10.3760/cma.j.cn511374-20250711-00421","DOIUrl":"10.3760/cma.j.cn511374-20250711-00421","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the clinical phenotype and molecular genetic characteristics of intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities (MRD50) due to variants of NAA15 gene.</p><p><strong>Methods: </strong>A retrospective analysis was carried out on the clinical data of four MRT50 pedigrees (7 patients in total) diagnosed at the Children's Hospital of Nanjing Medical University between February 2022 and August 2024. Pathogenic variants carried by the patients were screened through whole exome sequencing and validated by Sanger sequencing in the respective pedigrees. Bioinformatics tools including MaxEntScan, dbscSNV, RDDC, and SpliceAI were employed to predicted the pathogenicity of splice-site variants. The functional impact of the c.692-5A>G splice-site variant was assessed by reverse transcription-PCR (RT-PCR) combined with agarose gel electrophoresis. PyMOL software was used to predict three-dimensional conformational changes of the variant proteins. Additionally, quantitative real-time PCR (qPCR) was applied to determine the mRNA expression of the NAA15 gene in the peripheral blood sample from the patients. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202402022-1).</p><p><strong>Results: </strong>The patients (3 males and 4 females), with a last follow-up age ranging from 5-year-and-1-month-old to 35 year old, exhibited varying degrees of intellectual disability, language delay, and learning difficulties. Among them, 3 cases were accompanied by motor developmental delay, 1 case by seizure onset, 1 case by attention-deficit/hyperactivity disorder, 1 case by autism spectrum symptoms, and 1 case by ventricular septal defect. Genetic testing has identified four heterozygous variants in the NAA15 gene, including one case with c.822_823insTA (p.E275*) nonsense variant, two cases with c.376_379delCAAAinsTCCTTACTACAGGT (p.Q126Sfs*9) frameshift variant caused by a complex indel, three cases with c.1029_1038delAGAGTTAGTA (p.E344*) nonsense variant, and one case with a c.692-5A>G splice-site variant. Functional analysis demonstrated that all variants has led to protein truncation. The c.692-5A>G variant may cause aberrant splicing. And the expression level of NAA15 mRNA in patients with the c.692-5A>G variant was significantly lower than the healthy controls.</p><p><strong>Conclusion: </strong>Variants of the NAA15 gene, including c.822_823insTA (p.E275*), c.376_379delCAAAinsTCCTTACTACAGGT (p.Q126Sfs*9), c.1029_1038delAGAGTTAGTA (p.E344*), and c.692-5A>G, may lead to MRD50. The core clinical manifestations are intellectual disability and language developmental delay, frequently accompanied by behavioral abnormalities and motor dysfunction.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"408-414"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844193","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":"[Experience with stem cell collection for children with Transfusion-dependent thalassemia undergoing gene therapy].","authors":"Meiping Liu, Yueyue Liang, Wenyan Long, Yujiao Luo, Li Wang, Rongying Gong, Rongrong Luo, Liping Huang","doi":"10.3760/cma.j.cn511374-20250616-00372","DOIUrl":"10.3760/cma.j.cn511374-20250616-00372","url":null,"abstract":"<p><strong>Objective: </strong>To explore the characteristics and strategies of stem cell collection in children with Transfusion-dependent thalassemia (TDT) undergoing gene therapy.</p><p><strong>Methods: </strong>To summarize the challenges encountered and the countermeasures taken during stem cell collection in 13 TDT children undergoing gene therapy at the Department of Pediatrics, 923rd Hospital of the Joint Logistics Support Force of PLA between August 2020 and January 2024.</p><p><strong>Results: </strong>Among the 13 TDT children, one required 1 collection, nine required 2 collections, one required 3 collections, and one required 4 collections. Adequate cells were collected in 12 cases, while 1 case had failed to obtain sufficient CD34+ cells despite multiple rounds of collection. The stem cell collection process was smooth in all 13 cases, with no adverse reactions.</p><p><strong>Conclusion: </strong>The stem cell mobilization regimen for TDT children needs to be enhanced, and saturated blood transfusion should be performed prior to stem cell collection.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"473-475"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844280","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 diagnosis and genetic analysis of 13 fetuses with 16p11.2 microdeletion/microduplication].","authors":"Xiaoduan Wang, Kai Zhang, Jiashan Li, Yanping Chen","doi":"10.3760/cma.j.cn511374-20251106-00647","DOIUrl":"10.3760/cma.j.cn511374-20251106-00647","url":null,"abstract":"<p><strong>Objective: </strong>To explore the ultrasound finding, pregnancy outcome, and follow-up of fetuses with 16p11.2 microdeletion/microduplication to provide a basis for genetic counseling.</p><p><strong>Methods: </strong>Thirteen fetuses with 16p11.2 microdeletion/microduplication detected by chromosomal microarray analysis (CMA) at the Genetic Testing Center of Women's and Children's Hospital Affiliated to Qingdao University between January 2021 and March 2024 were selected as study subjects. Prenatal ultrasound finding, results of genetic testing and family verification, pregnancy outcome, and postnatal conditions were retrospectively analyzed. Data were analyzed using descriptive statistical analysis. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: QFELL-YJ-2024-159).</p><p><strong>Results: </strong>Among 4 985 fetuses undergoing prenatal diagnosis, 13 (0.26%) were detected with 16p11.2 microdeletion/microduplication. Among these, 8 were microdeletions with a size ranging from 0.174 Mb to 0.84 Mb, and 5 were microduplications with a size ranging from 0.59 Mb to 0.89 Mb. The main prenatal ultrasound findings included cardiovascular abnormalities, vertebral developmental abnormalities, and nuchal translucency thickening. Parental tracing was performed in 12 of the 13 fetuses, with five cases verified to have a de novo origin, and seven originated from a phenotypically normal parent. Following genetic counseling, eight couples had opted induced labor, one couple with twin pregnancy had selected reduction of the abnormal fetus, whilst four couples had chosen to continue with the pregnancy. At follow-up, the liveborn infants were aged between 16 and 26 months, with one diagnosed with congenital heart disease, one with infantile epilepsy, and two showing no abnormality in growth and development.</p><p><strong>Conclusion: </strong>CMA testing holds a significant value for the prenatal diagnosis of 16p11.2 microdeletion/microduplication. For fetuses with positive results, it is necessary to consult and conduct long-term follow-up in conjunction with prenatal ultrasound and parental tracing results in order to provide appropriate guidance for pregnancy decision and selection of reproductive methods.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"415-421"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844290","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 Chinese pedigree affected with Charcot-Marie-Tooth disease presenting as childhood-onset encephalopathy].","authors":"Haitong Zheng, Binglong Huang, Yinhui Chen, Siqi Chen, You Wang, Yongwen Lin, Chengyan Li","doi":"10.3760/cma.j.cn511374-20250725-00456","DOIUrl":"10.3760/cma.j.cn511374-20250725-00456","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotypes and genetic characteristics of a Chinese pedigree affected with X-linked Charcot-Marie-Tooth disease (CMTX) with childhood-onset episodic encephalopathy as the initial manifestation.</p><p><strong>Methods: </strong>Clinical data and auxiliary examination results of a pedigree with \"limb weakness, dysarthria and dysphonia\" presented at the Affiliated Hospital of Guangdong Medical University between April 2023 and December 2024 were retrospectively analyzed. The proband and other pedigree members underwent whole exome sequencing. Candidate variants were subsequently validated within the pedigree by Sanger sequencing. In addition, literature search and summary analysis were carried out using keywords including \"X-linked Charcot-Marie-Tooth disease type 1,\" \"children,\" and \"GJB1 gene\" in the China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, and PubMed databases. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: YJYS2022352).</p><p><strong>Results: </strong>The pedigree has comprised five affected individuals from three generations. The probands were monozygotic male twins with the onset age of 10 and 11 years, respectively, without preceding infection. Both child had presented with limb weakness, dysarthria, and dysphonia as initial symptoms, which were improved with treatment. Brain MRI revealed bilateral frontoparietal white matter lesions. Electromyography demonstrated peripheral neuropathy in the four limbs. Whole exome sequencing identified a c.224G>A (p.Arg75Gln) missense variant in the GJB1 gene, which was inherited from the mother. The variant was classified as pathogenic based on the guidelines from American College of Medical Genetics and Genomics (ACMG) (PS3+PS4+PM2_Supporting+PM5+PP3), confirming the diagnosis of CMTX1. No symptom has occurred during the follow-up, and repeat brain MRI one year post-onset showed complete resolution of the abnormalities. Literature review has identified 18 male pediatric CMTX1 cases presenting with encephalopathy as the initial manifestation. Episodic limb weakness, dysarthria, and facial palsy were the main clinical manifestations. MRI predominantly showed transient hyperintense signals in the periventricular deep white matter, centrum semiovale, and splenium of corpus callosum, which resolved spontaneously within weeks to months.</p><p><strong>Conclusion: </strong>For male pediatric patients presenting with episodic encephalopathy, peripheral neuropathy, and transient white matter abnormalities on brain MRI, CMTX1 should be suspected. Early implementation of neurophysiological studies and GJB1 gene testing is crucial for timely diagnosis, precise management, and accurate genetic counseling.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"422-427"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844177","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 characterization and genetic analysis of two Chinese pedigrees affected with Familial adenomatous polyposis caused by variants of MUTYH gene].","authors":"Long Zhang, Yuhou Shen, Hualing Duan, Hongyang Qi, Aimin Yue","doi":"10.3760/cma.j.cn511374-20250920-00557","DOIUrl":"10.3760/cma.j.cn511374-20250920-00557","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotypes and genetic characteristics of two patients with Familial adenomatous polyposis (FAP) due to variants of MUTYH gene.</p><p><strong>Methods: </strong>Two patients presenting with multiple colorectal polyps on gastrointestinal endoscopy at Xinxiang Central Hospital respectively in June and October 2022 were selected as study subjects. A retrospective study design was employed to collect their clinical data and summarize their clinical and genetic features. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were validated by Sanger sequencing of their family members. Bioinformatic analysis was conducted for the candidate variants. Pathogenicity of the variants was assessed based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital [Ethics No.: 2024-282-01 (K)].</p><p><strong>Results: </strong>Patient 1 was a 7-year-old girl who presented with \"pigmentation on the lips, buccal mucosa, hard palate, eyelids and fingers for 5 years.\" Colonoscopy revealed multiple colonic polyps. WES revealed that she has harbored compound heterozygous variants of the MUTYH gene, namely c.857G>A (p.Gly286Glu) and c.1118C>T (p.Ala373Val), which were inherited from her mother and father, respectively. Based on the ACMG guidelines, the variants were classified as pathogenic (PS4+PM1+PM2_Supporting+PP3) and variant of uncertain significance (VUS) (PM2_Supporting+PP3), respectively. Patient 2 was a 42-year-old male who presented with \"increased frequency of bowel movements for 2 month.\" Colonoscopy revealed multiple colorectal polyps. WES revealed that he has harbored compound heterozygous variants of the MUTYH gene, namely c.53C>T (p.Pro18Leu) and c.880C>T (p.Arg294Cys), which were inherited from his father and mother, respectively. Based on the ACMG guidelines, the variants were classified as likely pathogenic (PS4+PM1+PM2_Supporting+PP3) and VUS (PM2_Supporting+PM1), respectively.</p><p><strong>Conclusion: </strong>Compound heterozygous variants of the MUTYH gene probably underlay the pathogenesis of FAP in these patients. Above findings have enriched the mutational spectrum of the MUTYH gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"466-472"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844285","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 testing and reproductive intervention for 210 Chinese pedigrees affected with Hemophilia].","authors":"Yi Zhang, Xiao Hu, Jing Dai, Zhengxing Wan, Juan Du, Liang Hu, Yueqiu Tan, Fei Gong, Guangxiu Lu, Ge Lin, Wenbin He","doi":"10.3760/cma.j.cn511374-20251212-00715","DOIUrl":"10.3760/cma.j.cn511374-20251212-00715","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology of 210 Chinese pedigrees affected with Hemophilia and provide prenatal diagnosis and preimplantation genetic testing (PGT) for them.</p><p><strong>Methods: </strong>A total of 210 unrelated pedigrees diagnosed with Hemophilia (176 with Hemophilia A and 34 with Hemophilia B) at the Reproductive and Genetic Hospital of CITIC-Xiangya between 2011 and 2024 were selected as study subjects. Genetic testing was carried out on the probands, including whole-exome sequencing, PCR-Sanger sequencing, and detection of intron 22 and intron 1 inversions of the F8 gene. Pathogenicity of candidate variants was classified based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). After the determination of genetic causes, reproductive intervention was implemented through prenatal diagnosis or preimplantation genetic testing (PGT). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010).</p><p><strong>Results: </strong>In total 137 pathogenic or likely pathogenic variants of the F8 and F9 genes were identified among 207 pedigrees (detection rate = 98.5%), among which 16 were were unreported previously. Respectively, 105 pathogenic or likely pathogenic variants (including 13 novel ones) of the F8 gene were detected among 174 pedigrees with Hemophilia A, while 32 pathogenic or likely pathogenic variants (including 3 novel ones) of the F9 gene were identified among 33 pedigrees with Hemophilia B. Among the 207 pedigrees, 65 had opted for prenatal diagnosis, and 9 fetuses were diagnosed with Hemophilia, and the pregnancies were terminated. On the other hand, 71 pedigrees had opted PGT, with 454 embryos from 90 cycles completed testing, which yielded a diagnostic rate of 99.8% (453/454). As a result, 100 healthy infants were born through reproductive intervention.</p><p><strong>Conclusion: </strong>This study has clarified the genetic basis of 207 pedigrees affected with Hemophilia. The results had expanded the mutational spectrum, and reduced the birth rate of Hemophilia by prenatal diagnosis and PGT.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"401-407"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844342","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 a child with Coffin-Siris syndrome type 8 due to an intronic variant of SMARCC2 gene].","authors":"Shiling Zhong, Yunyan Li, Yuanling Chen, Haibo Li, Changshui Chen, Ling Wu, Lulu Yan","doi":"10.3760/cma.j.cn511374-20250812-00483","DOIUrl":"10.3760/cma.j.cn511374-20250812-00483","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic characteristics of a child with Coffin-Siris syndrome type 8 (CSS8) due to an intronic variant of the SMARCC2 gene.</p><p><strong>Methods: </strong>A child who had attended the Women and Children's Hospital of Ningbo University on 5 March, 2025 was selected as study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and her family members. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants was validated by Sanger sequencing. The effect of candidate variants on mRNA was analyzed using an in vitro minigene assay. CSS8-related publications were searched in home and oversea databases for a literature review. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094).</p><p><strong>Results: </strong>The child had manifested intellectual disability, delayed language development, recurrent fever, rash, joint pain, and chronic multifocal aseptic osteomyelitis. WES revealed that she has harbored a heterozygous c.1496+2T>C variant of the SMARCC2 gene, which may affect the splicing of mRNA. Sanger sequencing verified that neither of her parents has carried the same variant. In vitro minigene assay indicated that the variant can affect the normal splicing of SMARCC2 mRNA and result in two abnormal transcripts including retaining of 126 bp upstream of intron 16 and skipping of exon 16. Both splicing forms did not alter the reading frame, but resulted in production of truncated proteins. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2_Moderate+PVS1_Moderate+PM2_Supporting+PS1_Supporting). The child was treated with naproxen and adalimumab, though she still had repeated episodes of attacks. After hormone supplementation and methotrexate treatment, her condition was relieved.</p><p><strong>Conclusion: </strong>The c.1496+2T>C variant of the SMARCC2 gene probably underlay the pathogenesis of CSS8 in this child. Above finding has enriched the mutational and phenotypic spectra of the SMARCC2 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 6","pages":"443-449"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844173","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}