中华医学遗传学杂志最新文献

{"title":"[Guidelines for the diagnosis, treatment, and management of Citrin deficiency (2026 Edition)].","authors":"Division Of Biochemistry And Metabolism Medical Genetics Branch Chinese Medical Association, Division Of Genetics And Metabolism Child Diseases And Health Care Branch Chinese Association For Maternal And Child Health Care, Xinwen Huang","doi":"10.3760/cma.j.cn511374-20251121-00678","DOIUrl":"10.3760/cma.j.cn511374-20251121-00678","url":null,"abstract":"<p><p>Citrin deficiency is an inherited metabolic disease that primarily affects the liver, growth and development, and can even lead to death. To deepen the understanding of this disease and improve the diagnostic and therapeutic levels as well as the standardized management of doctors in the relevant fields in China, this \"Guidelines for the diagnosis, treatment, and management of Citrin deficiency\" have been formulated. This guideline can provide opinions over eight clinical issues related to the diagnosis, treatment, and management of Citrin deficiency based on the currently available clinical evidence.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 2","pages":"81-89"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150874","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 phenotype and genetic analysis of two fetuses with Osteocraniostenosis due to variants of FAM111A gene].","authors":"Lingyi Zhang, Zhigang Zhang, Xingguang Wang, Yanyan Li","doi":"10.3760/cma.j.cn511374-20251030-00635","DOIUrl":"10.3760/cma.j.cn511374-20251030-00635","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the prenatal manifestation and genetic basis for two fetuses suspected for Osteocraniostenosis (OCS).</p><p><strong>Methods: </strong>Two fetuses undergoing invasive prenatal diagnosis at Cangzhou People's Hospital in April and August 2021 for short long bones and abnormal skull morphology were selected as the study subjects. Clinical data were collected and analyzed. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the two couples. Candidate variants were validated by Sanger sequencing. Literature was retrieved from CNKI, Wanfang Data Knowledge Service Platform and PubMed using keywords including \"FAM111A gene\", \"gracile bone dysplasia\", \"FAM111A\" and \"osteocraniostenosis\" from January 1, 2000 to June 30, 2025. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K2020-049).</p><p><strong>Results: </strong>Fetus 1 was found to have short limbs, abnormal skull morphology and shallow cerebral sulci. Fetus 2 showed short limbs, irregular skull halo, prominent forehead and bilateral frontal narrowing. Trio-WES revealed that fetus 1 has carried a heterozygous missense variant c.1582G>C (p.Asp528His) in exon 4 of the FAM111A gene, which was unreported previously. Fetus 2 has harbored a heterozygous in-frame deletion c.1020_1022delTTC (p.Ser343del) in exon 6 of the FAM111A gene, which has been recorded as likely pathogenic by the ClinVar and HGMD databases. Sanger sequencing confirmed that the parents of both fetuses were wild-type for the variant sites. A total of 9 previously reported patients with FAM111A-related gracile bone dysplasia/OCS from 4 publications were retrieved. The main clinical features included intrauterine growth restriction, hypomineralized skull, gracile long bones with narrow medullary cavities and characteristic facial anomalies, which were in large in keeping with the prenatal features of the two fetuses.</p><p><strong>Conclusion: </strong>Both fetuses were diagnosed with FAM111A-related OCS based on the characteristic prenatal findings and identification of the FAM111A variants. Above finding expanded the phenotypic spectrum of FAM111A-associated disorders and provided clues for the prenatal diagnosis and genetic counseling.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 2","pages":"96-101"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150797","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 three-generation Chinese pedigree affected with Hereditary spastic paraplegia type 3A due to variant of ATL1 gene].","authors":"Zhenhua Gong, Fengjuan He, Changshui Chen, Yu An","doi":"10.3760/cma.j.cn511374-20251021-00619","DOIUrl":"10.3760/cma.j.cn511374-20251021-00619","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation.</p><p><strong>Methods: </strong>A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated 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.: 2025-12).</p><p><strong>Results: </strong>A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic.</p><p><strong>Conclusion: </strong>The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 2","pages":"129-135"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150886","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":"[Research progress on the molecular genetic mechanism of Parkinson's disease].","authors":"Wei Quan","doi":"10.3760/cma.j.cn511374-20251021-00617","DOIUrl":"10.3760/cma.j.cn511374-20251021-00617","url":null,"abstract":"<p><p>The pathogenesis of Parkinson's disease is closely related to genetic factors. This article has systematically reviewed the research progress of molecular genetic mechanism on Parkinson's disease by focusing on the role of six high-penetrance pathogenic genes (SNCA, LRRK2, PRKN, PINK1, PARK7, and VPS35) and some risk genes (such as GBA1). These genetic variants eventually converge in three core pathogenic biological pathways, including lysosomal-autophagy pathway disorder, mitochondrial quality control disorder and α-synuclein metabolic abnormality. In-depth understanding of these molecular mechanisms is of great significance for the development of targeted therapy and realization of precision medicine for this disease.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 2","pages":"151-157"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150856","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":"[Pontocerebellar hypoplasia type 2B due to compound heterozygous variants of TSEN2 gene: A case report and literature review].","authors":"Xueqin Lin, Hailan He, Saying Zhu, Yulin Quan, Shichen Zhou, Zhanwei Zhang, Jing Peng","doi":"10.3760/cma.j.cn511374-20250805-00478","DOIUrl":"10.3760/cma.j.cn511374-20250805-00478","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical and genetic features of a child with Pontocerebellar hypoplasia type 2B (PCH2B) due to compound heterozygous variants of the TSEN2 gene.</p><p><strong>Methods: </strong>A PCH2B patient presented at Department of Pediatric Neurology, Xiangya Hospital of Central South University in June 2023 was selected as the study subject. Clinical data of the patient were retrospectively analyzed. The patient and her parents were subjected to whole exome sequencing and bioinformatic analysis. Pathogenicity of the candidate variants were classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang Data, and PubMed databases from their establishment to May 2025 using keywords \"TSEN2 gene\" \"PCH2B\" and \"Pontocerebellar Hypoplasia 2B\" to summarize the clinical and genotypic features of patients with PCH2B due to variants of the TSEN2 gene. This study was approved by the Medical Ethics Committee of the Hospital (No.: #202310892).</p><p><strong>Results: </strong>The patient, a 6-year-5-month-old girl, had exhibited severe global developmental delay, developmental regression, autism spectrum disorder, myoclonus of eyelids, feeding difficulty, irritability, progressive microcephaly, esotropia, and hypotonia. MRI showed reduced volume of bilateral cerebellar hemispheres and vermis. Genetic testing revealed that she has harbored compound heterozygous variants of the TSEN2 gene (NM_025265.4), namely c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile), which were inherited from her father and mother, respectively. Both variants were classified as likely pathogenic based on the ACMG guidelines and were previously unreported. Literature review has identified six PCH2B patients with missense, nonsense, frameshift, and splice site variants of the TSEN2 gene. Their main clinical manifestations included global developmental delay, progressive microcephaly, feeding difficulties, irritability, and vermis hypoplasia. Cranial MRI and genetic testing are crucial for definite diagnosis.</p><p><strong>Conclusion: </strong>The c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile) compound heterozygous variants of the TSEN2 gene probably underlay the pathogenesis in this patient. Above findings has expanded the genotypic and phenotypic spectra of TSEN2-related PCH2B, and offered guidance for genetic counseling for this family.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 1","pages":"44-49"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100884","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 ultrasound manifestations and postnatal follow-up of fetuses with 22q11.2 microdeletion syndrome].","authors":"Xiaofei Liu, Ya'nan Wang, Tizhen Yan, Shengli Zhang, Yanchuan Xie, Jiwu Lou, Hongwei Jiang","doi":"10.3760/cma.j.cn511374-20250818-00492","DOIUrl":"10.3760/cma.j.cn511374-20250818-00492","url":null,"abstract":"<p><strong>Objective: </strong>To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition.</p><p><strong>Methods: </strong>Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed.</p><p><strong>Results: </strong>Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects.</p><p><strong>Conclusion: </strong>Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 1","pages":"31-35"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100805","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":"[Research advance on the clinical phenotypes and molecular genetic mechanisms of Microcephalic primordial dwarfism].","authors":"Linliang Hong, Ruimin Chen","doi":"10.3760/cma.j.cn511374-20251016-00609","DOIUrl":"10.3760/cma.j.cn511374-20251016-00609","url":null,"abstract":"<p><p>Primordial dwarfism (PD) refers to a group of monogenic genetic disorders characterized by intrauterine growth restriction (IUGR) and severe, persistent postnatal growth retardation. These diseases have been associated with variants of multiple genes whose products are mainly involved in critical cellular biological processes such as maintenance of genomic stability, DNA damage repair, mRNA splicing regulation, and centrosome function. Variants of such genes can directly impair cell proliferation and developmental potential. With the widespread application of molecular genetic technologies such as high-throughput sequencing, significant progress has been made in the research of PD. This article focuses on the major subtypes of PD, including Seckel syndrome, Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, MOPD type II, and Meier-Gorlin syndrome. It has systematically summarized the advances in their clinical phenotypic characteristics, pathogenic genes, and molecular mechanisms, with an aim to deepen the understanding of the essence of growth disorders associated with PD.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 1","pages":"76-80"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100841","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 child with 46,XX male phenotype due to SOX3 gene duplication].","authors":"Xiou Wang, Fuying Song, Ziqin Liu, Pengchao Wang, Mu Du, Yi Song, Shuyue Huang, Bingyan Chao","doi":"10.3760/cma.j.cn511374-20250814-00488","DOIUrl":"10.3760/cma.j.cn511374-20250814-00488","url":null,"abstract":"<p><strong>Objective: </strong>To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene.</p><p><strong>Methods: </strong>A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056).</p><p><strong>Results: </strong>The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered.</p><p><strong>Conclusion: </strong>Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 1","pages":"50-56"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100658","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":"[Precise identification of a cryptic balanced translocation in a couple with recurrent spontaneous abortions using C-MoKa technique].","authors":"Rui Fan, Yaru Liu, Tingting Ji, Xiaojuan Xu, Xuening Ding, Xiaoling Ma","doi":"10.3760/cma.j.cn511374-20250911-00539","DOIUrl":"10.3760/cma.j.cn511374-20250911-00539","url":null,"abstract":"<p><strong>Objective: </strong>Chromosome conformation-based karyotype analysis (C-MoKa) technology was used to test a couple who had experienced multiple adverse pregnancies in order to provide them with genetic counseling and reproductive guidance.</p><p><strong>Methods: </strong>A couple presented at the Reproductive Medicine Center of the First Hospital of Lanzhou University in 2023 was selected as the study subject. Through C-MoKa testing, copy number variation sequencing (CNV-seq), and preimplantation genetic testing for aneuploidy (PGT-A), it was found that the couple's repeatedly miscarried fetuses and abnormal embryos exhibited highly similar chromosomal structural abnormalities. Using C-MoKa, the potential genetic abnormalities in both partners were traced, and reproductive guidance was provided based on the result. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-09).</p><p><strong>Results: </strong>CNV-seq analysis of the couple's miscarriage fetal chorionic villi showed del(18)(q21.2q23)(28.90 Mb) and dup(13)(q31.2q34)(26.26 Mb). Chromosomal karyotyping analysis of both partners showed no abnormality. From 2024 to 2025, the couple underwent three rounds of PGT-A assisted reproduction. The first embryo test showed del(13)(q31.2q34)(26.77 Mb) and dup(18)(q21.2q23)(29.08 Mb). The second embryo test showed dup(13)(q31.2q34)(26.26 Mb) and del(18)(q21.2q23)(28.90 Mb). And the third embryo test results showed complex chromosomal abnormalities. In 2025, after genetic counseling, the couple had opted C-MoKa test, which has detected no abnormality in the wife, but a balanced 46,XY,t(13;18)(q31.2;q21.2) translocation in the husband.</p><p><strong>Conclusion: </strong>As a high-throughput sequencing method based on the three-dimensional conformation of chromatin, C-MoKa has the advantages of high resolution and high accuracy, and can accurately detect balanced translocations with similar banding patterns. It has therefore offered a powerful new tool for chromosomal analysis.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 1","pages":"64-69"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100793","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":"[Development and validation of PhenoRAG: A visualization tool for automated human phenotype ontology term annotation based on large language models and retrieval-augmented generation technology].","authors":"Wei Zhong, Yousheng Yan, Kai Yang, Yan Liu, Xinyu Fu, Zhengyang Yao, Chenghong Yin","doi":"10.3760/cma.j.cn511374-20250923-00564","DOIUrl":"10.3760/cma.j.cn511374-20250923-00564","url":null,"abstract":"<p><strong>Objective: </strong>To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset.</p><p><strong>Methods: </strong>By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application \"RAG-HPO\". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset.</p><p><strong>Results: </strong>An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038).</p><p><strong>Conclusion: </strong>Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"43 1","pages":"36-43"},"PeriodicalIF":0.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100755","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}