中华医学遗传学杂志最新文献

{"title":"[Precise genetic analysis and reproductive guidance for two rare families with complex chromosomal rearrangements facilitated by optical genome mapping].","authors":"Jiangyang Xue, Min Xie, Yuxin Zhang, Yingwen Liu, Haibo Li","doi":"10.3760/cma.j.cn511374-20250408-00212","DOIUrl":"10.3760/cma.j.cn511374-20250408-00212","url":null,"abstract":"<p><strong>Objective: </strong>To apply optical genome mapping (OGM) technique for the analysis of genetic etiology in two rare families with complex chromosomal rearrangements (CCRs) and to provide precise reproductive guidance to them.</p><p><strong>Methods: </strong>Two Chinese families diagnosed with chromosomal rearrangements by chromosomal microarray analysis (CMA) or whole-exome sequencing (WES) between June and December 2023 at the Affiliated Women and Children's Hospital of Ningbo University were selected as the study subjects. In both cases, unbalanced chromosomal translocations were suspected. Clinical data were collected, and peripheral blood from the couple, amniotic fluid sample and aborted fetal tissue was subjected to combined G-banding karyotyping and OGM for comprehensive genetic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2023-094).</p><p><strong>Results: </strong>In family 1, the fetus was signaled to have abnormal chromosome 7 by non-invasive prenatal testing (NIPT), prompting amniocentesis and CMA detection. In family 2, a pregnancy loss had occurred at 10 weeks' gestation, and trio-WES was carried out. Both fetuses were found to harbor copy number variations (CNVs) suggestive of unbalanced CCRs. Further analysis with OGM has revealed that, in family 1, an unbalanced rearrangement involving chromosomes 7, 8, and 10 was carried by the fetus and the pregnant woman, which has formed der(8) and der(10) derivative chromosomes. In family 2, a maternal CCR was found, which involved chromosomes 2 and 13 with seven breakpoints, resulting in unbalanced fetal CNVs. After genetic counseling, family 1 opted to continue with the pregnancy, considering the woman's normal appearance and inheritance of the rearrangement. For both families remained to have a risk for unbalanced rearrangements in subsequent pregnancies, preimplantation genetic testing (PGT) was recommended.</p><p><strong>Conclusion: </strong>In both families, the OGM has precisely delineated the genetic basis of fetal CNVs and mapped the maternal CCR breakpoints, providing critical insights for genetic counseling and reproductive decision-making.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 7","pages":"883-889"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065918","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 genotypic analysis of a four-generation Chinese pedigree affected with Stickler syndrome and a literature review].","authors":"Wenjun He, Fang Tang, Fan Jiang, Ziman Chen, Yan Lu, Yutong Ni, Jianying Zhou, Dongzhi Li","doi":"10.3760/cma.j.cn511374-20250418-00235","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20250418-00235","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C&gt;T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C&gt;T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"684-690"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790277","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":"[Chitayat syndrome due to variant of ERF gene: A case report and literature review].","authors":"Guanming Li, Yuanhong Ji, Airun Zhang, Mengting Yang, Xiaoyi Fang","doi":"10.3760/cma.j.cn511374-20241202-00629","DOIUrl":"10.3760/cma.j.cn511374-20241202-00629","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical features and management of a child with Chitayat syndrome.</p><p><strong>Methods: </strong>A child presented at the Fengqing People's Hospital on August 8 2019 was selected as the study subject. Clinical data of the child were retrospectively analyzed. Peripheral blood samples were collected from the child and his father and sister. Whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genome Browser, AlphaFold, and PolyPhen-2 were employed for protein structure simulation and amino acid sequence conservation analysis. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Literature was retrieved from databases including CNKI, Wanfang, and PubMed using the keyword \"Chitayat syndrome\". The clinical characteristics and prognosis of patients with Chitayat syndrome were reviewed and analyzed. This study was approved by the Ethics Committee the Seventh Affiliated Hospital of Sun Yat-sen University (Ethics No.: KY-2024-086-01).</p><p><strong>Results: </strong>The child was born at full term and had special facial features, skeletal abnormalities, recurrent respiratory tract infections and global developmental delay. WES and Sanger sequencing revealed that he has harbored a heterozygous c.266A>G p.(Tyr89Cys) variant of the ERF gene. Protein structure modeling suggested that the mutant protein has increased spatial distance between the side chain group and DNA, which may reduce its binding affinity to DNA. Amino acid sequence analysis indicated that the p.Tyr89 residue is highly conserved across multiple species. The variant was therefore classified as pathogenic (PM1+PM2_Supporting+PM6+PS1+PP3). The patient was diagnosed with \"Chitayat syndrome\". Nutritional support and rehabilitation training were recommended, though the child had died of severe pneumonia at 13 months old. Literature retrieval has collected 7 relevant articles, which involved 14 cases of Chitayat syndrome confirmed by genetic testing. Together with our case, all patients had facial dysmorphisms and skeletal deformities. Fourteen patients (93.3%) had respiratory distress. Seven of them (46.7%) had recurrent respiratory infections and 7 (46.7%) were confirmed with respiratory tract malacia. Eight (53.3%) patients had neuropsychological retardation, while 8 (53.3%) had growth delay. The main interventions for Chitayat syndrome include respiratory and nutritional support, and rehabilitation training for developmental delays.</p><p><strong>Conclusion: </strong>Chitayat syndrome is rarely seen and its clinical manifestations may vary. Airway management and early intervention of developmental delay are important for improving the prognosis.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"729-735"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790274","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":"[SETD1B gene related epilepsy and language delay: A case report and literature review].","authors":"Xiaoli Zhang, Mingyue Jin, Mengyue Wang, Na Ma, Jinshuang Gao, Jialin Li, Yichao Ma","doi":"10.3760/cma.j.cn511374-20240621-00348","DOIUrl":"10.3760/cma.j.cn511374-20240621-00348","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay.</p><p><strong>Methods: </strong>A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using \"SETD1B\" and \"epilepsy\" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024.</p><p><strong>Results: </strong>The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females.</p><p><strong>Conclusion: </strong>SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"713-718"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790281","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 treatment of two children with Lesch-Nyhan syndrome].","authors":"Guang'e Yang, Conglei Song, Fan He, Kaili Zhang, Bin Yang","doi":"10.3760/cma.j.cn511374-20241010-00527","DOIUrl":"10.3760/cma.j.cn511374-20241010-00527","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To explore the clinical, genetic, therapeutic and prognostic characteristics of two children with Lesch-Nyhan syndrome (LNS) in order to enhance understanding of this disease and formulate more effective therapeutic strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical data were collected from two children clinically diagnosed with LNS who were treated at Anhui Provincial Children's Hospital from April 2023 to January 2024. Data were retrospectively collected and included clinical manifestations (symptoms, signs, laboratory and imaging findings), treatment course, and results of follow-up. Peripheral venous blood samples were obtained from child 1 and his parents. Whole-exome sequencing (WES) was performed. Candidate variants were validated by Sanger sequencing. Standard bioinformatic analysis of the raw WES data was conducted, including quality control, alignment, variant calling, and annotation. Candidate pathogenic variants were filtered using population frequency databases (e.g., gnomAD), disease databases (e.g., OMIM, ClinVar), and multiple in silico pathogenicity prediction tools (e.g., SIFT, PolyPhen-2, CADD). Phenotype matching was integrated using Human Phenotype Ontology (HPO) terms. Pathogenicity classification of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (2015). This study was approved by the Medical Ethics Committee of Anhui Children's Hospital, Children's Hospital of Fudan University (Ethics No.: EYLL-2014-027).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Child 1, a 4-year-old boy, had presented with developmental delay for over 3 years, accompanied by abnormal postures and involuntary lip-biting. Physical examination revealed limb dystonia, anxious expression, lower lip damage, and communication difficulties. Laboratory tests showed hyperuricemia and renal stones. Genetic testing identified a hemizygote variant of the HPRT1 gene, c.135G&gt;T (p.Arg45Ser), inherited from an asymptomatic carrier mother, which confirmed the diagnosis of LNS. This variant was absent from population databases (gnomAD, 1000 Genomes, dbSNP). Protein function prediction tools consistently indicated it as a pathogenic or likely pathogenic variant (SIFT, PolyPhen-2, CADD, and REVEL scores all reached pathogenic thresholds). Protein structural modeling revealed that the variant may disrupt the hydrogen-bonding network compromising the tetramer stability. ACMG classification designated it as likely pathogenic (PM1+PM2_Supporting+PM5+PP3). The patient was treated with benhaxol hydrochloride, baclofen, and clonazepam to improve his neurological symptoms, in addition with treatment with febuxostat from the Nephrology Department to manage his purine metabolism. After one year of follow-up, the patient's abnormal posture showed slight improvement, self-injurious behavior persisted but was managed with protective gloves, blood ur","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"691-699"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790276","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":"[Gene sequencing analysis and protein structural modeling for a case with Aw26 subtype of the ABO blood group].","authors":"Qianqian Chen, Jinrong Chen, Kaizhao Huang, Jiajin Lin","doi":"10.3760/cma.j.cn511374-20240704-00372","DOIUrl":"10.3760/cma.j.cn511374-20240704-00372","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the sequencing results, protein structure model, and impact of mutations on the dynamic stability of glycosyltransferase (GTA) in a case with Aw26 blood group subtype.</p><p><strong>Methods: </strong>ABO phenotype was determined by serological testing (anti-A, anti-B, anti-H, and reverse typing). Potential variant of the ABO gene was identified by Sanger sequencing, and the haploid sequence of the variant site was analyzed by TOPOT-A cloning. Molecular models of the GTA was generated by PyMol, and 100-ns molecular dynamics (MD) was simulated with GROMACS software to assess the conformational stability using root mean square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bonding, and binding free energy.</p><p><strong>Results: </strong>Serological assays confirmed the proband as an Aw subtype, whose genotype was identified as ABO*Aw.26/ABO*O.01.02 with variants including p.Pro156Leu, p.Arg176His and p.Pro354ArgfsTer23. Haploid sequencing validated the results of direct sequencing. Molecular modeling showed that the p.Arg176His variant could reduce water-mediated hydrogen bonds from six (wild-type) to one (variant). MD simulation revealed the wild type system could achieve equilibrium within 10 ns (mean RMSD ≈ 0.30 nm), whilst the mutant system required 50 ns to equilibrate and exhibited greater fluctuation (mean RMSD ≈ 0.40 nm). Root mean square fluctuation (RMSF) analysis confirmed significantly increased flexibility in the mutant's N-terminal loop (residues 63-76). The mutant Rg displayed an expansion-contraction transition within 0 ~ 40 ns, and its SASA value has increased. The number of hydrogen bonds and binding energy of the mutant had decreased (wild-type: 5 to 8, binding energy: -11.53 kcal/mol; mutant: 2 to 5, binding energy:-8.52 kcal/mol).</p><p><strong>Conclusion: </strong>An Aw26 subtype was identified. The p.Arg176His and p.Pro354Argfs*23p variants could synergistically compromise the structural stability of GTA and its substrate binding capacity by disrupting the hydrogen-bond network, increasing local flexibility, and reducing the overall conformational stability.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"667-674"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790279","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 phenotype and genetic variant in a patient with De-differentiated liposarcoma].","authors":"Jingjing Ao, Feicheng Yang, Yuzhong Yang, Jia Tian, Chenjia Lu, Xiaoying Liu, Zhe Zhang, Wenxiu Yang, Chunjian Mo","doi":"10.3760/cma.j.cn511374-20250320-00168","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20250320-00168","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic etiology of a patient with De-differentiated liposarcoma (DDLPS).</p><p><strong>Methods: </strong>A 38-year-old female patient with DDLPS who had visited Hunan Provincial People's Hospital in January 2025 was selected as the study subject. A retrospective study method was adopted to collect the patient's clinical data, including current and past medical history, auxiliary examinations, pathological diagnosis, and results of genetic testing. This study was approved by the Ethics Committee of Hunan Provincial People's Hospital (Ethics No.: KY2025-150).</p><p><strong>Results: </strong>The patient had presented with abdominal pain and abdominal mass. Imaging studies revealed ascites and space-occupying abdominal lesions. Postoperative pathological examination showed that the tumor was composed of spindle cells, and its morphology and immunohistochemistry had made it difficult to distinguish between DDLPS and leiomyosarcoma. High-throughput sequencing revealed characteristic molecular alterations of DDLPS, and fluorescence in situ hybridization confirmed MDM2 gene amplification, leading to a diagnosis of DDLPS.</p><p><strong>Conclusion: </strong>The patient was diagnosed with DDLPS. Her clinical manifestations and pathological features were consistent with the characteristics of DDLPS. Molecular pathological testing played a crucial role in the diagnosis and provided a crucial reference for subsequent treatment.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"741-746"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790242","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":"[Association between genotype and phenotype in children with Phenylalanine hydroxylase deficiency in Lianyungang area].","authors":"Shuang Liu, Qin Zheng, Dandan Cui, Wei Wang, Leilei Wang, Guanghua Luo","doi":"10.3760/cma.j.cn511374-20241125-00620","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241125-00620","url":null,"abstract":"<p><strong>Objective: </strong>To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.</p><p><strong>Methods: </strong>Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041).</p><p><strong>Results: </strong>PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001).</p><p><strong>Conclusion: </strong>PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"648-659"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Analysis of a child with Congenital leukemia and mosaicism trisomy 21 syndrome without GATA1 gene mutation].","authors":"Liya Zhang, Yu Liu, Yu Ding, Lulu Yan, Fei Li, Qingqing Jie, Shuni Sun, Lili Chen, Xiamin Jin","doi":"10.3760/cma.j.cn511374-20250611-00359","DOIUrl":"10.3760/cma.j.cn511374-20250611-00359","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL).</p><p><strong>Methods: </strong>A child who was admitted to Ningbo Women and Children's Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063).</p><p><strong>Results: </strong>Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia.</p><p><strong>Conclusion: </strong>For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"751-755"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790239","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 neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome and a literature review].","authors":"Dandan Wang, Qianqian Li, Hongxiang Guo, Qingfei Hao, Yongning Chen, Xiuyong Cheng","doi":"10.3760/cma.j.cn511374-20250317-00161","DOIUrl":"10.3760/cma.j.cn511374-20250317-00161","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR).</p><p><strong>Methods: </strong>A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University on December 6,2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using \"hypoparathyroidism\"\"sensorineural deafness\"\"renal dysplasia\"\"HDR\"\"Barakat\" and\"GATA3\" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025.</p><p><strong>Results: </strong>A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously.</p><p><strong>Conclusion: </strong>For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 6","pages":"700-706"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790240","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}