中华医学遗传学杂志最新文献

{"title":"[Clinical phenotype and genetic analysis of a child with CAKUTHED syndrome due to variant of PBX1 gene].","authors":"Jiao Tang, Chuan Zhang, Ruiqiong Yang, Xinyuan Tian, Bingbo Zhou, Yupei Wang, Ling Hui","doi":"10.3760/cma.j.cn511374-20241015-00535","DOIUrl":"10.3760/cma.j.cn511374-20241015-00535","url":null,"abstract":"<p><p>OBJECTIVE：To explore the clinical characteristics and genetic etiology of a child with CAKUTHED syndrome.</p><p><strong>Methods: </strong>A child who was admitted to the neonatal department of Gansu Provincial Maternal and Child Health Care Hospital due to \"neonatal asphyxia\" in May 2021 was selected as the study subject. Genomic DNA was extracted from peripheral venous blood samples from the child and his parents, and whole exome sequencing (WES) was carried out. Sanger sequencing was used to verify the candidate variant of the PBX1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: 2021GSFY (65)].</p><p><strong>Results: </strong>The proband, a male neonate, manifested renal dysplasia, congenital heart disease, pulmonary dysplasia, mediastinal hernia, cryptorchidism, and clavicle dysplasia. WES revealed that he had harbored a heterozygous c.863G>A (p.Arg288Gln) missense variant in exon 6 of PBX1 gene, which resulted substitution of Arginine at position 288 by Glutamine, for which both parents were of the wild type. The variant was unreported previously and rated as pathogenic (PS2+PM1+PM2_Supporting+PP2+PP3) based on the ACMG guidelines.</p><p><strong>Conclusion: </strong>The c.863G>A variant of the PBX1 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PBX1 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1471-1476"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436524","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 features and genetic analysis of a child with STISS syndrome due to variant of PSMD12 gene].","authors":"Delong Peng, Chunxiao Han, LuLu Yan, Haibo Li, Haiya Yan","doi":"10.3760/cma.j.cn511374-20250225-00107","DOIUrl":"10.3760/cma.j.cn511374-20250225-00107","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic etiology of STISS syndrome (an autosomal dominant disorder characterized by ubiquitin-proteasome system dysfunction) in a child.</p><p><strong>Methods: </strong>A child with STISS syndrome diagnosed at the Affiliated Women and Children's Hospital of Ningbo University in September 2024 due to \"abnormal development of external genitalia\" was selected as the study subject. Clinical data were retrospectively collected. Peripheral blood samples were obtained from the child and his family members. Following genomic DNA extraction, whole-exome sequencing (WES) and Sanger sequencing validation were carried out. Pathogenicity of the candidate variants was assessed based on the guidelines from American College of Medical Genetics and Genomics (ACMG). The study was approved by the Ethics Committee of the hospital (Ethics No.: EC2023-094).</p><p><strong>Results: </strong>The proband, a 16-year-old boy, presented with micropenis, testicular hypoplasia, delayed sexual development, insulin resistance, diabetes mellitus, and obesity. WES revealed that he has harbored a c.934del; p.Met312TrpfsTer3 frameshifting variant of the PSMD12 gene, which was unreported previously. Sanger sequencing confirmed that the variant to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_supporting+PM6_supporting). The variant was predicted to result in a premature termination codon. Bioinformatics analysis suggested that the amino acid at position 312 is highly conserved, and the variant may therefore affect the protein structure.</p><p><strong>Conclusion: </strong>Patients with STISS syndrome exhibit clinical features including psychomotor retardation, intellectual disability, distinctive facial features, and urogenital abnormalities. The c.934del (p.Met312TrpfsTer3) frameshift variant of the PSMD12 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PSMD12 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1459-1464"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436492","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 phenotype and genetic analysis of a fetus with abnormal development due to a rare paternal t(10;14)(p11.2;p11) translocation].","authors":"Fengni Fan, Rong Qiang, Cuiyun Qin, Rui Wang","doi":"10.3760/cma.j.cn511374-20241022-00550","DOIUrl":"10.3760/cma.j.cn511374-20241022-00550","url":null,"abstract":"<p><strong>Objective: </strong>To explore a case of abnormal fetal development due to a rare paternal t(10;14)(p11.2;p11) translocation.</p><p><strong>Methods: </strong>A fetus undergoing prenatal diagnosis at Northwest Women's and Children's Hospital on June 21,2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample of the fetus and peripheral venous blood samples of its parents were collected for chromosomal karyotyping and copy number variation (CNV) analysis. This study was approved by the Ethics Committee of the hospital (Ethics No.: 2024-132).</p><p><strong>Results: </strong>Ultrasound scan at 23⁺⁴ gestational weeks revealed nasal bone dysplasia. Amniotic fluid analysis revealed that the fetus has a karyotype of 46,X?,der(14)t(10;14)(p11.2;p11)dpat, while its father had a 46,XY,t(10;14)(p11.2;p11) karyotype. No chromosomal abnormality was found in its mother. CNV analysis revealed that the fetus had a 30.46 Mb duplication in the 10p15.3-p11.23 region. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the duplication was classified as pathogenic.</p><p><strong>Conclusion: </strong>By combining conventional cytogenetic methods with molecular techniques, the fetus was diagnosed with partial trisomy 10p syndrome caused by a rare paternal t(10;14)(p11.2;p11) translocation. Above finding holds significant clinical value for genetic counseling and prenatal diagnosis for the family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1508-1512"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436502","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 clinical features and genetic variants in a Chinese pedigree affected with Spondyloepiphyseal dysplasia type Ehlers-Danlos syndrome due to variants of B3GALT6 gene].","authors":"Shaocong Lan, Chengyan Li, Binglong Huang, Yinhui Chen, Zaoye Xie, Wenhao Deng, Dang Ao","doi":"10.3760/cma.j.cn511374-20250112-00025","DOIUrl":"10.3760/cma.j.cn511374-20250112-00025","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for \"delayed motor development for 1 and a half year\" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C&gt;T (p.Arg256Trp) and c.962G&gt;A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C&gt;T and c.962G&gt;A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C&gt;T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C&gt;T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G&gt;A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have include","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1482-1489"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436432","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 Chinese pedigree affected with Isolated growth hormone deficiency due to variant of CHRHR gene].","authors":"Hui Yin, Bingyan Cao, Ziqin Liu, Fuying Song, Ying Liu, Yi Liu, Xiaobo Chen","doi":"10.3760/cma.j.cn511374-20250424-00249","DOIUrl":"10.3760/cma.j.cn511374-20250424-00249","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD).</p><p><strong>Methods: </strong>A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033).</p><p><strong>Results: </strong>The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function.</p><p><strong>Conclusion: </strong>Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1446-1452"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436509","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":"[Advance in research on MIRAGE syndrome].","authors":"Zhiqiang Qin, Xiaomin Zhang","doi":"10.3760/cma.j.cn511374-20251022-00621","DOIUrl":"10.3760/cma.j.cn511374-20251022-00621","url":null,"abstract":"<p><p>MIRAGE syndrome is a rare autosomal dominant disorder caused by gain-of-function mutations of the SAMD9 gene. Its typical clinical manifestations include myelodysplasia, intrauterine growth restriction, adrenal hypoplasia, genital abnormalities, and enteropathy. The gain-of-function toxicity of the SAMD9 gene and subsequent somatic revertant mutations have been identified as the core molecular mechanisms underlying the multi-system phenotypes and clonal hematopoietic evolution in this disease. The specific genotypic background and tissue-specific distribution of somatic revertant mutations collectively constitute the genetic basis for its significant clinical heterogeneity. In recent years, important breakthroughs have been made in research on the pathogenesis, phenotypic expansion, molecular diagnosis, and targeted therapy of the MIRAGE syndrome. This article has systematically reviewed the latest progress made in the research on the etiology, clinical manifestations, diagnosis, and treatment of this disease.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1513-1517"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436394","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 the distribution frequencies of HLA-A and HLA-B alleles in patients with immune-mediated Platelet transfusion refractoriness].","authors":"Ying Liu, Zuonian Xie, Heqiong Liu, Xianguo Xu, Wei Zhang, Faming Zhu","doi":"10.3760/cma.j.cn511374-20250515-00298","DOIUrl":"10.3760/cma.j.cn511374-20250515-00298","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the distribution frequency and characteristics of HLA-A and HLA-B loci in patients with immune-mediated Platelet transfusion refractoriness (iPTR) in order to provide data support for investigating HLA gene matching strategies for platelet transfusion and improving transfusion efficacy.</p><p><strong>Methods: </strong>A total of 532 iPTR patients who applied for gene matched platelet at the Blood Center of Zhejiang Province between January 2020 and June 2024 were selected as the study subjects. Genomic DNA was extracted from peripheral blood samples from the patients, and the HLA-A and HLA-B loci were detected simultaneously using a PCR-sequence specific oligonucleotide probe method (PCR-SSO) and PCR-sequence based typing (PCR-SBT). Statistical methods were used to analyze the distributions of HLA-A and HLA-B antigens and genotypes on the platelet surface of the patients. An analysis of the differences was conducted to compare the results with the Common and Well-Documented (CWD) allele in the Chinese population from the China Marrow Donor Program (CMDP) database. This study was approved by the Medical Ethics Committee of the Blood Center of Zhejiang Province (Ethics No.: Provincial Blood Center Ethics Review 2023Yan No.004).</p><p><strong>Results: </strong>Among the 532 iPTR patients, 19 HLA-A antigens (including 32 HLA-A alleles) and 37 HLA-B antigens (including 64 HLA-B alleles) were detected. The antigens with the highest frequencies were A2, A11, A24, and B46, B60, B58, with the combined distribution frequency of the top three antigens reaching 71.43% and 36.94%, respectively. The most prevalent alleles of the HLA-A and HLA-B loci were A*11:01, A*24:02, A*02:07 and B*46:01, B*40:01, B*58:01. The frequencies of common alleles A*01:01, A*02:07, A*11:02, A*30:01 and B*13:02, B*27:04, B*40:01, B*44:03, B*46:01 showed significant differences (P < 0.05) compared to the normal population in the CWD table (version 2.4) of CMDP.</p><p><strong>Conclusion: </strong>The HLA-A and HLA-B genes of the iPTR patients showed great divergence, and the distribution frequencies of certain alleles have differed significantly from those of the normal population. This study has provided genetic data for exploring the molecular mechanism underlying iPTR, which is of significant clinical importance for searching HLA gene matched donors.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1415-1423"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436480","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":"[Identification and functional analysis of a novel variant of CHD23 gene in a Chinese pedigree affected with Non-syndromic autosomal recessive deafness 12].","authors":"Litao Qin, Zengguo Ren, Meiying Wang, Tingting Shi, Xin Chen, Qian Zhang, Guiyu Lou, Shixiu Liao, Li Wang","doi":"10.3760/cma.j.cn511374-20250514-00290","DOIUrl":"10.3760/cma.j.cn511374-20250514-00290","url":null,"abstract":"<p><strong>Objective: </strong>To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms.</p><p><strong>Methods: </strong>A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134).</p><p><strong>Results: </strong>WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents.</p><p><strong>Conclusion: </strong>The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1490-1495"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436529","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 features and genetic etiology analysis in a patient with Fliedner-Zweier syndrome caused by a de novo SCAF4 variant].","authors":"Lulu Yan, Changshui Chen, Yuxin Zhang, Juan Cao, Chunxiao Han, Haibo Li","doi":"10.3760/cma.j.cn511374-20250415-00227","DOIUrl":"10.3760/cma.j.cn511374-20250415-00227","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic etiology of a patient with Fliedner-Zweier syndrome (FZS).</p><p><strong>Methods: </strong>A pregnant woman who was diagnosed with FZS at the Affiliated Women and Children's Hospital of Ningbo University in November 2023 for \"intellectual disability, epilepsy, delayed language development and facial abnormalities\" was selected as the study subject. Peripheral blood samples were collected from the woman and her husband, whilst amniotic fluid sample was obtained from the fetus. Following extraction of genomic DNA, whole-exome sequencing (WES) and chromosomal karyotyping analysis were performed. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094).</p><p><strong>Results: </strong>The proband, a 23-year-old woman, was at 19⁺² weeks of gestation and had a history of epilepsy, mild intellectual disability, delayed language development, and subtle facial dysmorphism. Chromosomal analysis showed the she has a normal karyotype. WES revealed that the woman and her fetus both harbored a heterozygous c.1489C>T (p.Gln497Ter) nonsense variant of the SCAF4 gene, which was verified by Sanger sequencing as de novo. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_supporting+PS2_supporting). According to pre-set search strategy, five articles were retrieved. Together with the patient in this study, a total of 69 FZS patients were involved (including 7 from China). The main clinical features have included intellectual disability, epilepsy, behavioral abnormalities, and facial dysmorphism.</p><p><strong>Conclusion: </strong>The heterozygous c.1489C>T (p.Gln497Ter) variant of the SCAF4 gene probably underlyay the FZS in this patient. Above finding has expanded the mutational spectrum of the SCAF4 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1453-1458"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436521","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 phenotypically normal male with SRY gene-positive 46,XX/46,XY tetrameric chimerism].","authors":"Weiguo Zhang, Mengxue Wu, Zhi Yang, Feiyan Pan, Zhizhi He, Yiyang Zhu","doi":"10.3760/cma.j.cn511374-20250313-00153","DOIUrl":"10.3760/cma.j.cn511374-20250313-00153","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical characteristics and genetic etiology of a male with a normal phenotype and SRY gene-positive 46,XX/46,XY tetrazoospermia chimerism.</p><p><strong>Methods: </strong>A male patient with an abnormal peripheral blood chromosomal karyotype detected at the Infertility Center of Taizhou Hospital of Zhejiang Province on December 2, 2013 was selected as the study subject. Peripheral venous blood samples were collected from the proband and his family members, together with a semen sample from the proband. Chromosomal karyotype analysis, red blood cell blood group identification, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), sex-determining region Y (SRY) gene detection, and short tandem repeat (STR) microsatellite marker analysis were performed on the peripheral venous blood sample from the proband. Routine semen analysis, sperm FISH, and STR testing were also conducted. STR verification was performed on both parents. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: k20201009).</p><p><strong>Results: </strong>The proband, a 37-year-old male, had normal secondary sexual characteristics and external genitalia development. The chromosomal karyotype of his peripheral blood sample was 46,XX[94]/46,XY[6]. ABO blood group typing was positive for Rh(D) type O and negative for Rh(D) type A, indicating the presence of two red blood cell populations. CMA result was arr[GRCh37](1-22)×2,(XX)×1. Autosomal and X chromosome SNP genotypes were BB-BB, AB-AB, and AA-AA, making it impossible to identify homozygous/heterozygous chimerism. FISH detection of interphase nuclei showed nuc ish XX[92]/XY[8]. Testing of the SRY gene was positive. STR analysis showed a single X peak (no Y peak) at the AMEL locus, 10/12 at the Penta D locus, and no third allele at other loci. Routine semen analysis were normal. Sperm FISH detection showed haploid nuclei nuc ish X[53]/Y[47]. Sperm STR analysis revealed an X/Y bimodal distribution at the AMEL locus and a 9/14 distribution at the Penta D locus, with no third allele observed at other loci. Above results suggested that the proband's blood and germ cell lines had originated from a heterozygous chimera formed by the fusion of two different zygotes.</p><p><strong>Conclusion: </strong>Combined genetic techniques confirmed that the proband's peripheral blood AMEL genotype is X/X, while the sperm is X/Y. The Penta D locus showed a bi-allelic heterozygous pattern of 10/12 in the peripheral blood sample and 9/14 in the sperm sample, suggesting that the proband is a tetrazygotic chimera resulted from the fusion of 46,XX/46,XY zygotes.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 12","pages":"1502-1507"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436459","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}