中华医学遗传学杂志最新文献

{"title":"[Study of 12 blood donors with c.389T>C variant of ABO*A1.01 allele and weak expression of A from Xi'an area].","authors":"Qinqin Zuo, Liangzi Zhang, Hua Xu, Yong Zhang","doi":"10.3760/cma.j.cn511374-20240812-00435","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240812-00435","url":null,"abstract":"<p><strong>Objective: </strong>To carry out serological and molecular tests on 12 blood donors and family members of one proband with discrepancy results for ABO serological typing.</p><p><strong>Methods: </strong>Twelve blood donors with ABO discrepancies identified by the Blood Center of Shaanxi Province from March 2015 to December 2023 and family members of one proband were selected as the study subjects. Serological blood typing was carried out to determine their blood phenotype. ABO genotype of the samples was determined by direct sequencing of amplicons of exons 1 to 7 and cloning sequencing of amplicons of exons 6 and 7. This study has been approved by the Ethics Committee of Blood Center of Shaanxi Province (202328).</p><p><strong>Results: </strong>Serological results showed that 5 samples were Aweak, 4 samples were Aweak with anti-A1 antibody, and 3 samples were AweakB with anti-A1. Direct sequencing and cloning sequencing results showed that all 12 samples had the haplotype ABO*A1.01/c.389T>C, and family studies showed that the allele could be stably inherited. Glycosyltransferase activity in the plasma was decreased in all samples.</p><p><strong>Conclusion: </strong>The c.389T>C variant of the ABO*A1.01 allele can alter the encoded amino acid p.Leu130Pro, which weakens the activity of A glycosyltransferase, ultimately leading to the weak expression of A antigen.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"406-410"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486428","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":"[Results of screening and prenatal diagnosis for 71 fetuses with high risk for trisomy/monosomy 13 syndrome by non-invasive prenatal screening].","authors":"Peng Dai, Ganye Zhao, Yanjie Xia, Xiangdong Kong","doi":"10.3760/cma.j.cn511374-20250113-00028","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20250113-00028","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT).</p><p><strong>Methods: </strong>Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08).</p><p><strong>Results: </strong>71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography.</p><p><strong>Conclusion: </strong>The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"397-405"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486427","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":"[Application value of chromosomal microarray analysis for the detection of low-level mosaicisms in amniotic fluid samples and analysis of rare cases].","authors":"Huiyuan Shao, Zongyu Miao, Hong Wu, Lei Li, Xiaoyan Liu, Yuping Wang, Lihua Jiang","doi":"10.3760/cma.j.cn511374-20241225-00685","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241225-00685","url":null,"abstract":"<p><strong>Objective: </strong>To assess the value of chromosomal microarray analysis (CMA) for the detection of low-level mosaicisms in amniotic fluid samples, and to retrospectively analyze the rare cases of mosaicisms.</p><p><strong>Methods: </strong>Chromosomal karyotype of the fetus was determined by G-banding analysis of cultured amniotic fluid cells. CMA was used to detect copy number variation of fetal chromosomes, and fluorescence in situ hybridization (FISH) was used to determine the proportion of fetal chromosomal mosaicisms in uncultured amniotic fluid cells.</p><p><strong>Results: </strong>Among 825 prenatal samples, 4 cases of true fetal mosaicisms were detected, which yielded an incidence of 0.48%. Two cases were sex chromosomal mosaicisms, and two were autosomal mosaicisms, which involved chromosomes 8 and 9, respectively. All cases were verified by G-banding analysis of cultured amniotic fluid cells, CMA, and/or FISH.</p><p><strong>Conclusion: </strong>CMA has a great value for detecting low-level mosaicisms in amniotic fluid samples, though the positive results need to be verified by other techniques and should be interpreted with caution. The review of rare cases can provide a basis for prenatal genetic counseling.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"441-445"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486414","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 child with gastrointestinal hemorrhage and Cerebroretinal microangiopathy with calcifications and cysts and a literature review].","authors":"Tao Jiang, Shuangjie Li, Yanfang Tan, Wenxian Ouyang","doi":"10.3760/cma.j.cn511374-20240620-00345","DOIUrl":"10.3760/cma.j.cn511374-20240620-00345","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic cause of a child with gastrointestinal hemorrhage and Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) and to review the literature.</p><p><strong>Methods: </strong>Clinical data of a child with gastrointestinal hemorrhage with CRMCC admitted to the Hepatology Department of Hunan Children's Hospital in September 2019 were collected, and peripheral blood DNA of the child and his parents were analyzed by whole exome sequencing. Candidate variants were validated by Sanger sequencing, followed by bioinformatics analysis, American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants pathogenicity classification, and protein structure prediction. A literature search with \"Coats Plus syndrome\" or \"Cerebroretinal microangiopathy with calcifications and cysts\" as keywords was conducted at PubMed, China National Knowledge Infrastructure and Wanfang databases to include recently published studies (up to December 2023). This study has been approved by the Ethics Committee of Hunan Children's Hospital (Ethics No. KY2020-07). Informed consent for clinical research was obtained from the guardian of the child.</p><p><strong>Results: </strong>The proband was a 10-year-10-month-old boy. The clinical manifestations were intrauterine and postnatal growth retardation, gastrointestinal hemorrhage, liver fibrosis, panhemopenia, bilateral exudative retinopathy, intracranial lesions and facial pigmentation. WES and Sanger sequencing revealed two novel heterozygous variants in the CTC1 gene: c.787G>A (p.Val263Met) in exon 5 and c.2930C>G (p.Ser977Cys) in exon 17, which were inherited from his mother and father, respectively. According to ACMG pathogenicity classification, both missense variants were classified as variants of uncertain significance (VUS). Protein structure prediction showed the absence of LIG_SH3_3 motif and LIG_SH3_3 motif, and the p.Ser977Cys mutation may affect the binding between CST (CTC1-STN1-TEN) complex and DNA strand. The child had continued to experience recurrent gastrointestinal bleeding episodes despite propranolol treatment, but the condition was controlled after liver transplantation. According to the predefined literature search strategy of this study, a total of 10 relevant articles on pediatric CRMCC patients were retrieved, involving 11 children with gastrointestinal bleeding. Pharmacological and endoscopic therapies play a certain role in the management of CRMCC children complicated with gastrointestinal bleeding.</p><p><strong>Conclusion: </strong>The CTC1 gene c.787G>A and c.2930C>G variants probably underlay CRMCC in this child. This study has broadened the variation spectrum of CTC1-related diseases and provided a basis for genetic counseling. Liver transplantation may be an important treatment for gastrointestinal hemorrhage in children who do not respond well to medi","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"486-494"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486422","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 Dent disease due to hemizygous variant of the CLCN5 gene].","authors":"Fengxun Liu, Cien Wei, Dongwei Liu","doi":"10.3760/cma.j.cn511374-20241231-00696","DOIUrl":"10.3760/cma.j.cn511374-20241231-00696","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical features and molecular etiology of a patient with Dent disease due to variant of CLCN5 gene.</p><p><strong>Methods: </strong>A male patient with Dent disease diagnosed at the First Affiliated Hospital of Zhengzhou University in September 2023 was selected as the study subject. Clinical data of the patient were collected. Whole exome sequencing (WES) was carried out for the patient and his family members. Pathogenicity of candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. KS-2018-KY-36).</p><p><strong>Results: </strong>The patient, a 15-year-old male, was admitted due to proteinuria and hematuria. Ultrasonography showed diffuse echogenic changes in both kidneys. Renal biopsy revealed structural dysfunction of renal tubules. Electron microscopy revealed minor tubular and glomerular lesions. The patient was found to harbor a hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene, which was derived from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PM2). Bioinformatic analysis using multiple software predicted the deleterious effect of the variant.</p><p><strong>Conclusion: </strong>The hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene probably underlay the pathogenesis of Dent disease in this patient. Above finding has enriched the mutational spectrum of the CLCN5 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"469-473"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486415","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":"[Expert consensus on the clinical application of Single-Molecule Real-Time Sequencing in the precise prevention and control of Thalassemia (2025 Edition)].","authors":"Consortium For The Application Of Single-Molecule Real-Time Sequencing For The Precision Medicine And Control Of Thalassemia, Group Of Clinical Genetics Medical Genetics Branch Of Chinese Medical Doctor Association, Lingqian Wu","doi":"10.3760/cma.j.cn511374-20250322-00173","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20250322-00173","url":null,"abstract":"<p><p>Thalassemia is a highly prevalent genetic hemoglobinopathy, with approximately 350 million people worldwide carrying variants of the globin genes. The carrier rate in southern China is as high as 10% ~ 25%. The \"multi-level sequential screening and diagnosis\" approach, which uses hematological screening, hotspot mutation testing, and genetic testing based on other technologies to diagnose rare types of thalassemia, has proven to be highly effective for the prevention and control of thalassemia. However, its cumbersome process, high cost for testing and medical labor, and high demand for genetic consulting have obvious limitations. For its advantages of long reads and accurate identification of sequence variants, Single-Molecule Real-Time (SMRT) Sequencing technology can not only broaden the scope of globin gene mutation detection, but also directly distinguish the haplotypes and structural rearrangements of the α- and β-globin genes, significantly improving the detection rate, reducing false positives and missed detection, and has revolutionized the detection for genetic variants underlying thalassemia. With the maturity of technology and decrease in cost, the application of SMRT sequencing in the prevention and control of thalassemia is becoming increasingly widespread. So far more than 50 clinical studies and 300,000 clinical application data have been accumulated. Based on these evidence-based studies, this consensus has explored the application scope, workflow, and limitations of employing SMRT sequencing in clinical genetic testing for thalassemia. It aims to provide recommendations and guidance for clinicians, laboratory staff, and policy makers, to support precise prevention and control of thalassemia throughout the full life cycle.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"385-396"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486420","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 family with Dentinogenesis imperfecta type Ⅰ caused by a novel mutation in the COL1A2 gene].","authors":"Zhuang Liu, Zhihui Zhang, Qin Wang, Qianqian Qin, Aijun Yang","doi":"10.3760/cma.j.cn511374-20250218-00084","DOIUrl":"10.3760/cma.j.cn511374-20250218-00084","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical phenotype and genetic characteristics of a family with Dentinogenesis imperfecta type Ⅰ(DGI-Ⅰ).</p><p><strong>Methods: </strong>Clinical data were collected from a patient with DGI-Ⅰ admitted to the Reproductive Medicine Department of the Affiliated Hospital of Jining Medical University in March 2024. Clinical and familial data were retrospectively collected. Peripheral blood samples (5 mL each) were obtained from the proband and her family members for genomic DNA extraction, followed by whole-exome sequencing (WES) and Sanger sequencing validation. The pathogenicity of the detected variants was assessed according to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the \"ACMG Guidelines\"). The study was approved by the Ethics Committee of the Affiliated Hospital of Jining Medical University (Ethics No. 2024-08-C012), and written informed consent for clinical research were obtained from all participants.</p><p><strong>Results: </strong>The proband, a 35-year-old female, presented with translucent yellow primary teeth and progressive browning, darkening, and loss of permanent teeth, without skeletal abnormalities. Affected family members exhibited similar phenotypes. Genetic testing revealed a heterozygous COL1A2 variant (c.1503+1G>A) in the patient and other affected members, while unaffected family members all lacked this variant. Based on the ACMG Guidelines, this variant was classified as likely pathogenic (PM4 + PP1_Strong + PM2_Supporting).</p><p><strong>Conclusion: </strong>The COL1A2 c.1503+1G>A heterozygous variant is the disease-causing mutation in this family. Above finding has expanded the mutational spectrum of the COL1A2 gene and provided a basis for genetic counseling and diagnosis in similar cases.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"454-459"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486423","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 with Hereditary coagulation factor Ⅻ deficiency due to compound heterozygous variants of Ⅻ gene].","authors":"Haixiao Xie, Huanhuan Wang, Meina Liu, Huinan Xia, Yuan Chen, Kaiqi Jia, Lihong Yang, Mingshan Wang","doi":"10.3760/cma.j.cn511374-20220220-00117","DOIUrl":"10.3760/cma.j.cn511374-20220220-00117","url":null,"abstract":"<p><strong>Objective: </strong>To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis.</p><p><strong>Methods: </strong>A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17).</p><p><strong>Results: </strong>The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein.</p><p><strong>Conclusion: </strong>The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"282-285"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081178","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":"[Report and literature review of a familial case of autoinflammatory disease associated with RELA gene variant].","authors":"Yunyan Li, Yuxin Zhang, Shiling Zhong, Yuanling Chen, Ling Wu, Haibo Li","doi":"10.3760/cma.j.cn511374-20240330-00202","DOIUrl":"10.3760/cma.j.cn511374-20240330-00202","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature.</p><p><strong>Methods: </strong>A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children's Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole-exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords \"RELA\" \"NF-κB\" \"autoinflammatory disease\" \"tofacitinib\" \"sulfasalazine\" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048).</p><p><strong>Results: </strong>The child primarily manifested with recurrent fever, vomiting, and oral ulcers. WES identified a heterozygous nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Despite treatment with adalimumab and tocilizumab, the child's symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient's growth and development remained normal. A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting.</p><p><strong>Conclusion: </strong>The nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child's recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"336-342"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080025","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 TYR gene variant in a patient with Oculocutaneous albinism].","authors":"Xiaolei Jin, Hanbing Xie, Ping Wang, Shuo Yang, Jingqun Mai, Xiao Xiao, Shanling Liu","doi":"10.3760/cma.j.cn511374-20240928-00512","DOIUrl":"10.3760/cma.j.cn511374-20240928-00512","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic basis of a patient with suspected Oculocutaneous albinism (OCA).</p><p><strong>Methods: </strong>An OCA patient presented at the West China Second Hospital of Sichuan University and his mother were selected as the study subjects. Peripheral blood samples were collected for the extraction of, genomic DNA, and whole exome sequencing (WES) was carried out. Candidate variants were verified through specific primer amplification, Sanger sequencing, and agarose gel electrophoresis. Bioinformatic analysis and pathogenicity rating were conducted on the candidate variants. This study has been approved by the Medical Ethics Committee of West China Second Hospital (No. 2024-228).</p><p><strong>Results: </strong>Genetic testing revealed that the patient had harbored variants in exon 1 of the TYR gene, including a c.157G>T (p.G53C) missense variant and a c.609dup (p.A204fs) frameshifting variant. Specific primer amplification and Sanger sequencing, combined with agarose gel electrophoresis, confirmed that these are compound heterozygous variants. Based on the guidelines from the ACMG, the c.157G>T was rated as likely pathogenic, and c.609dup was rated as pathogenic. Alphafold3 predicted that the variant proteins had significant structural changes.</p><p><strong>Conclusion: </strong>The patient was diagnosed with OCA due to compound heterozygous variants of the TYR gene. Discovery of the c.609dup variant has enriched the mutational spectrum of OCA and provided a basis for genetic counseling and prenatal diagnosis for this patient.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"349-354"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081179","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}