中华医学遗传学杂志最新文献

{"title":"[Genetic analysis of a fetus with Short-rib thoracic dysplasia 8 with or without polydactyly due to variants of DYNC2I1 gene].","authors":"Yingwen Liu, Chunxiao Han, Yuxin Zhang, Lulu Yan, Jiangyang Xue, Haibo Li","doi":"10.3760/cma.j.cn511374-20250221-00099","DOIUrl":"10.3760/cma.j.cn511374-20250221-00099","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical characteristics of a fetus with Short-rib thoracic dysplasia 8 with or without polydactyly (SRTD8) due to variants of DYNC2I1 gene.</p><p><strong>Methods: </strong>A fetus identified to have short ribs, short long bones, and narrow thorax at 26<sup>+1</sup> weeks of gestation at the Women and Children's Hospital of Ningbo University in September 2024 was selected as study subject. The fetus underwent termination of pregnancy at 35<sup>+5</sup> weeks of gestation. Clinical data of the fetus were retrospectively collected. Whole exome sequencing (WES) was carried out on fetal tissue, and candidate variants were validated by Sanger sequencing. Difference between the wild type and variant DYNC2I1 proteins was analyzed using AlphaFold v3.0.1 and PyMOL v2.5.6 software. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using keywords such as \"DYNC2I1 gene\", previous literature on patients due to biallelic DYNC2I1 gene variants were retrieved from the PubMed databases, CNKI, and Wanfang Data Knowledge Service Platform, and the genetic variant and clinical phenotypes of patients were analyzed. The literature retrieval time was set from the establishment of database to December 31, 2025. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-094).</p><p><strong>Results: </strong>Prenatal ultrasound revealed that the fetus had short ribs, short long bones, and narrow thorax at 26<sup>+1</sup> gestational weeks. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the DYNC2I1 gene, namely c.265_268 (p.Gln89GlyfsTer15) in exon 3 and c.1777C>T (p.Arg593Trp) in exon 14, which were inherited from his father and mother, respectively. Prediction of the DYNC2I1 protein structure suggested that the c.265_268del variant has formed a premature termination codon, which may significantly alter the protein's secondary structure. The c.1777C>T variant may disrupt the electrostatic interaction between Arg593 and Asp729. Based on the ACMG guidelines, the c.265_268del (p.Gln89GlyfsTer15) variant was predicted to be likely pathogenic (PM2_Supporting +PVS1), whilst the c.1777C>T(p.Arg593Trp) variant was rated as uncertain significance (PM2_Supporting+PM3+PP4). Literature search has identified five articles related to biallelic DYNC2I1 variants involving a total of 11 fetuses/patients. Together with the fetus from this study, typical phenotypes included short ribs (6 cases), narrow thorax (6 cases), short limb bones (6 cases), and hand polydactyly (6 cases), and foot polydactyly (5 cases), albeit with significant clinical heterogeneity. A total of 12 genetic variants were identified, among which c.44delC was the most common (16.7%, 4/24), followed by c.1777C>T, c.2246C>T, and c.2305G>A (each accounting for 12.5%). No mutational hotspot was identified.</p><p><strong>Co","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 9","pages":"700-707"},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841535","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 prenatal and postnatal clinical features of six cases of Williams syndrome and a literature review].","authors":"Xinyue Liu, Xiaoyan Wang, Dan Sun, Qiongyan Li, Jingyue Liu, Pujie Huang","doi":"10.3760/cma.j.cn511374-20260327-00148","DOIUrl":"10.3760/cma.j.cn511374-20260327-00148","url":null,"abstract":"<p><strong>Objective: </strong>To review the clinical data of six cases of Williams syndrome (WS) and analyze the prenatal and postnatal diagnostic indications, genetic characteristics, and clinical manifestations, and review the relevant literature.</p><p><strong>Methods: </strong>Six cases of WS diagnosed at Maternal and Child Health Care Hospital of Hubei Province between January 2023 and December 2025 were selected as study subjects. Clinical data were collected, and chromosomal karyotyping, chromosomal microarray analysis (CMA), copy number variation sequencing (CNV-seq), and whole exome sequencing (WES) were carried out. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2026-146-01).</p><p><strong>Results: </strong>All of the six cases were found to have a deletion in the 7q11.23 region, with a size ranging from 0.75 Mb to 1.59 Mb. Indications for prenatal diagnosis included lateral ventricle enlargement (1 case), interrupted inferior vena cava (1 case), duodenal atresia (1 case), previous history of fetal growth retardation (1 case), and high-risk signaled by non-invasive prenatal testing (1 case). Family verification showed that in two cases the deletions were inherited from the mother, and in one case it was de novo. For the remaining three cases, parental verification was refused. A child diagnosed after birth carried a de novo 1.43 Mb deletion and presented with global developmental delay, dysmorphic facial features, and complex cardiac malformations.</p><p><strong>Conclusion: </strong>The prenatal manifestations of WS are diverse and non-specific. For cases with primary fetal growth retardation, cardiac structural abnormalities, and high-risk by NIPT, prenatal genetic testing should be recommended. Family verification can clarify the parental origin and assess the recurrence risk. Genetic techniques such as CNV-seq, CMA, and WES are of great value for the individualized management of affected children.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 9","pages":"666-672"},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841501","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 a fetus with mosaicism 3q26-qter duplication and 10q26-qter deletion].","authors":"Changtao Ke, He Wang, Shuping Zhang, Yun Huang, Song Ge, Xiaofeng Li","doi":"10.3760/cma.j.cn511374-20260323-00135","DOIUrl":"10.3760/cma.j.cn511374-20260323-00135","url":null,"abstract":"<p><strong>Objective: </strong>To analyze a fetus with a mosaicism unbalanced chromosomal translocation and explore its genetic mechanism and potential risks.</p><p><strong>Methods: </strong>A pregnant woman undergoing prenatal diagnosis at Peking University Shenzhen Hospital due to high-risk by Down syndrome screening was selected as study subject. With informed consent obtained, karyotyping analysis and chromosomal microarray analysis (CMA) were conducted on amniotic fluid cells and peripheral blood samples from the couple. Fluorescence in situ hybridization (FISH) was also performed on sperm sample from the husband. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2026-032).</p><p><strong>Results: </strong>Karyotyping analysis of amniotic fluid cells indicated a derivative chromosome 10, der(10)t(3;10), with a mosaicism level of 20%. CMA revealed a duplication of 3q26.32-q29 (mosaicism rate: 17%) and a deletion of 10q26.12-q26.3 (mosaicism rate: 18%). The karyotyping and CMA results of the couple were both normal. FISH analysis of the sperm did not detect signals for 3q27.3 duplication and 10q26.3 deletion.</p><p><strong>Conclusion: </strong>The mosaicism unbalanced chromosomal translocation in the fetus is a de novo rearrangement, and its phenotype exhibited heterogeneity.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 9","pages":"715-720"},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841539","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 Townes-Brocks syndrome due to a novel variant of SALL1 gene and a literature review].","authors":"Yunqian Chi, Futao Sun, Zihan Zhang, Yunhe Wang, Wei Hao","doi":"10.3760/cma.j.cn511374-20251219-00733","DOIUrl":"10.3760/cma.j.cn511374-20251219-00733","url":null,"abstract":"<p><strong>Objective: </strong>To analyze a novel exonic variant of the SALL1 gene and its impact on the binding site of SALL protein.</p><p><strong>Methods: </strong>Clinical data of three children diagnosed with Townes-Brocks syndrome and their family members who had presented at the First Affiliated Hospital of Shandong First Medical University in April 2022 were retrospectively collected. The pathogenic variant was identified through whole-genome sequencing (WGS) and validated by Sanger sequencing. Protein structural prediction was performed using AlphaFold and PyMOL software to construct three-dimensional models of the wild-type and mutant proteins. Additionally, previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-386).</p><p><strong>Results: </strong>The proband was one of triplet sisters born at 34⁺⁴ gestational weeks. All three cases had presented with anal atresia and rectovaginal fistula, and case 3 also had toe malformation of left foot. WGS revealed a novel heterozygous c.757C>T (p.Gln253*) variant in the SALL1 gene, which was predicted to be pathogenic. Sanger sequencing confirmed co-segregation of the variant with the disease within the family. Protein structural modeling demonstrated that the variant has introduced a premature stop codon at position 253, resulting in a truncated protein.</p><p><strong>Conclusion: </strong>Above finding has enriched the mutation spectrum of the SALL1 gene in association with Townes-Brocks syndrome, which also represented a rare case of anal atresia in triplets, and provided a basis for molecular diagnosis, genetic counseling, and further research.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 9","pages":"693-699"},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841529","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 diagnosis, exclusion, and follow-up for newborns with positive genetic screening results by next-generation sequencing (2026 Edition)].","authors":"Lianshu Han, Yonglan Huang, Jingkun Miao","doi":"10.3760/cma.j.cn511374-20260202-00061","DOIUrl":"10.3760/cma.j.cn511374-20260202-00061","url":null,"abstract":"<p><p>With the application of high-throughput sequencing technology in neonatal genetic disease screening, the scope of screened diseases has significantly expanded. However, after recall and further examination of positive screening results, physicians may encounter difficulties in the diagnosis, treatment, and follow-up. To tackle these, the Screening Group of Neonatal Genetic Metabolic Disease, Special Committee for Birth Defects Prevention and Control, Chinese Preventive Medicine Association has organized experts from relevant fields. By referencing domestic and international expert consensuses and research findings on disease diagnosis and treatment, a consensus has been formulated through multiple rounds of discussions. It has summarized the principles for confirming, excluding, and suspecting diagnoses in neonates with positive genetic screening results, with typical genetic diseases across different systems used as examples. These include genetic metabolic disorders, hematological genetic diseases, immunodeficiency disorders, neuromuscular genetic diseases, hereditary kidney diseases, hereditary hearing loss, and hereditary eye diseases. The aim is to provide standardized and practical guidance for neonatal genetic screening, promote standardized and efficient screening practices, improve early diagnosis rates for genetic diseases, further optimize follow-up and management strategies, and improve the prognosis of patients.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 9","pages":"641-656"},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841478","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":"[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].","authors":"Yijuan Huang, Yuanqiu Chen, Shaobin Lin, Zhiqiang Zhang, Chenyu Gou, Si Li, Xiaohong Wang, Tongtong Chen, Yu Gao, Weiying Jiang","doi":"10.3760/cma.j.cn511374-20240418-00241","DOIUrl":"10.3760/cma.j.cn511374-20240418-00241","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM).</p><p><strong>Methods: </strong>A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210).</p><p><strong>Results: </strong>G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10.</p><p><strong>Conclusion: </strong>The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 9","pages":"688-692"},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841488","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 child with Basel-Vanagaite-Smirin-Yosef syndrome due to variant of MED25 gene].","authors":"Yong Zhao, Nuo Li, Yu Han, Nannan Li, Qiuli Liu, Wenjie Fu, Guanjun Luo, Yizhao Chen, Nantian Wang, Yuan Zhou, Xuguang Qian","doi":"10.3760/cma.j.cn511374-2025-0327-00185","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-2025-0327-00185","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical features and genetic etiology of a child with Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS).</p><p><strong>Methods: </strong>A child diagnosed with BVSYS at Foshan Nanhai District Maternal and Child Health Care Hospital in January 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole genome sequencing (WGS) was carried out, and candidate variants were validated by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on 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.: 2025-01).</p><p><strong>Results: </strong>The proband, a 4-year-and-5-month-old boy, presented with global developmental delay with intellectual disability, characteristic facial features, speech impairment, abnormal muscle tone, epilepsy, congenital heart disease, abnormal brain MRI findings, and microcephaly. WGS revealed that he has harbored compound heterozygous variants of the MED25 gene: (NM_030973.3) c.180+5G>C (maternal) and (NM_030973.3) c.394C>G (p.Arg132Gly) (paternal). Transcriptome sequencing confirmed that the c.180+5G>C variant may cause aberrant splicing with retention of intron 2. Based on the ACMG guidelines, this variant met the criteria PS3+PM2_Supporting+PP3 and was classified as likely pathogenic. The c.394C>G (p.Arg132Gly) variant resulted in an amino acid substitution and was predicted to be deleterious by in silico analysis. Based on the ACMG criteria (PM2_Supporting+PMS+PP3), it was classified as a variant of uncertain significance. A literature review showed that, among 23 BVSYS patients reported between 2015 and 2025, the most common clinical manifestations were developmental delay/intellectual disability and characteristic facial features (100%), followed by speech impairment (78.3%), abnormal muscle tone (60.8%), ocular abnormalities (60.8%), epilepsy (47.8%), and cardiac anomalies (47.8%).</p><p><strong>Conclusion: </strong>The c.180+5G>C and c.394C>G compound heterozygous variants of the MED25 gene probably underlay the pathogenesis of BVSYS in this child.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 8","pages":"592-597"},"PeriodicalIF":0.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841498","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 Dyggve-Melchior-Clausen syndrome due to variant of DYM gene].","authors":"Haiyi Liu, Qianwen Zhang, Guoying Chang, Fan Yang, Juan Li, Qun Li, Shili Gu, Zhigang Wang, Ruen Yao, Tingting Yu, Xiumin Wang","doi":"10.3760/cma.j.cn511374-20250428-00261","DOIUrl":"10.3760/cma.j.cn511374-20250428-00261","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the clinical phenotype and genetic etiology of patients with Dyggve-Melchior-Clausen syndrome (DMC syndrome).</p><p><strong>Methods: </strong>A child with DMC syndrome diagnosed at Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University in August 2020 was selected as study subject. A retrospective analysis was carried out to collect the proband's clinical data. Peripheral blood samples was collected from the proband and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants were validated within the family by Sanger sequencing. Pathogenicity of candidate variants was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the center (Ethics No.: SCMCIRB-K2023024-1).</p><p><strong>Results: </strong>The proband, a 5-year-and-7-month-old girl, presented with short stature (height: -5.5 s) and intellectual disability. Physical examination revealed microcephaly (head circumference: -3.5 s), coarse facial features, long philtrum, pigeon chest, and brachydactyly of both hands. Laboratory findings revealed normal serum insulin-like growth factor-1 (IGF-1) levels (168 ng/mL). Imaging analysis demonstrated dysplasia of corpus callosum and spondyloepiphyseal dysplasia in the proband. WES revealed that she has harbored compound heterozygous variants of the DYM gene, namely c.312-313del (p.His104Glnfs*29) and c.1274A>T (p.Tyr425Phe). Both variants were unreported previously and inherited from her parents who were phenotypically normal. Based on guidelines from the ACMG, the DYM gene variant c.312-313del (p.His104Glnfs*29) was classified as pathogenic (PVS1+PM2_Supporting+PP3+PP4_supporting), while the c.1274A>T (p.Tyr425Phe) variant was classified as likely pathogenic (PM2_Supporting+PP3+PP1+PP4_supporting). By following the pre-set literature search strategy, a total of 20 articles were included, which involved a total of 73 cases of DYM gene variants leading to DMC syndrome. Among these, only one family case was documented in China. Together with proband from this study, a total of 74 DMC syndrome patients due DYM gene variants were included for a comprehensive analysis of clinical phenotypes and genetic characteristics. The age at the time of reporting ranged from 1 to 60 years. The main clinical manifestations included intellectual disability, short stature, and spondyloepiphyseal dysplasia, followed by microcephaly and coarse facial features. By genetic testing, c.1877delA variant was the most common mutation at the nucleotide level.</p><p><strong>Conclusion: </strong>The c.312-313del/c.1274A>T compound heterozygous variants of the DYM gene probably underlay the pathogenesis of DMC syndrome in this proband. Above finding has expanded the mutational and phenotypic spectra of the DMC syndrome.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 7","pages":"525-533"},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319633","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 genetics analysis of a fetus with type 27 intellectual disability syndrome due to variant of SRRM2 gene].","authors":"Chunxiao Han, Lulu Yan, Yuxin Zhang, Changshui Chen, Haibo Li","doi":"10.3760/cma.j.cn511374-20250507-00274","DOIUrl":"10.3760/cma.j.cn511374-20250507-00274","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and genetic etiology of a fetus with autosomal dominant intellectual disability type 72 (MRD72) resulting from a variant of the SRRM2 gene.</p><p><strong>Methods: </strong>A Chinese pedigree with MRD72 (fetus) who had visited the Affiliated Women and Children's Hospital of Ningbo University in November 2024 was selected as study subject. Clinical data of the pedigree were collected. Amniotic fluid and peripheral blood samples were collected from the fetus and its parents for genomic DNA extraction. Whole-exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing of the family members and rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on MRD72 were searched in domestic and international databases for a review. This study was approved by the hospital (Ethics No.: EC2023-094).</p><p><strong>Results: </strong>The proband was a fetus of 25 weeks of gestation. Fetal echocardiography revealed a relatively small left atrium and left ventricle, along with a diminished aortic-to-pulmonary artery ratio. WES revealed that the fetus has harbored a heterozygous nonsense variant of the SRRM2 gene. Sanger sequencing confirmed both parents carried the wild-type alleles. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+PM2_Supporting) and has not been recorded in public databases. Bioinformatic analysis predicted amino acid 512 to be highly conserved across various species. According to the pre-set literature search strategy, 4 publications were retrieved, which involved 30 MRD72 patients from 27 pedigrees, In addition to this study, a total of 31 cases were included. Analysis of clinical features and genetic etiology showed that patients with MRD72 presented mainly with clinical manifestations such as mental and motor development delay, special facial features, speech/intellectual development delay, and obesity. The genetic etiology was all variants at relevant loci of the SRRM2 gene.</p><p><strong>Conclusion: </strong>The SRRM2 variant identified in this study is implicated as the genetic cause of MRD72 in the proband. Above results have expanded the mutational and phenotypic spectra of the SRRM2 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 7","pages":"534-540"},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319631","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":"[Phenotypic modification of β-Thalassemia by variants of SUPT5H gene: Report of two pedigrees and a literature review].","authors":"Xiangyuan Huang, Lijuan Zhong, Rui Zhang","doi":"10.3760/cma.j.cn511374-20250425-00252","DOIUrl":"10.3760/cma.j.cn511374-20250425-00252","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the genetic and clinical characteristics of two Chinese pedigrees exhibiting β-thalassemia traits due to variants of SUPT5H gene and conduct a literature review.</p><p><strong>Methods: </strong>Two pregnant women and their family members with abnormal thalassemia screening results were selected as study subjects. Clinical data were collected, and peripheral blood DNA was extracted for thalassemia-targeted gene testing and whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants were rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also carried out on SUPT5H variants associated with thalassemia by searching the PubMed database. This study was approved by the Ethics Committee of Bao'an Women's and Children's Hospital [Ethics No.: LLSC-2025-02-05-15-KS].</p><p><strong>Results: </strong>Both probands exhibited mild anemia during pregnancy, which was characterized by typical hypochromic microcytic anemia, while no pathogenic variant was detected in the HBB gene. WES and Sanger validation of family members revealed two nonsense variants (SUPT5H: c.1195C>T, p.Gln399*) and (SUPT5H: c.397C>T, p.Arg133*) in the two pedigrees. Carriers from both pedigrees exhibited elevated hemoglobin A2 (Hb A2) and reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Literature review has identified 68 cases of SUPT5H gene variants involving 35 types. Nearly all carriers had elevated Hb A2 levels, 85.2% (58/68) carriers showed decreased MCV or MCH, and 3 cases with concurrent HBB gene variants exhibited significantly lower hemoglobin levels.</p><p><strong>Conclusion: </strong>Loss-of-function variants of the SUPT5H gene may cause β-thalassemia-like phenotypes through a haploinsufficiency mechanism. Routine screening for thalassemia modifier genes, including SUPT5H, is recommended for individuals with unexplained β-thalassemia phenotypes in high-prevalence areas to prevent the birth of children with moderate-to-severe thalassemia.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 7","pages":"511-517"},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319568","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}