Human molecular genetics最新文献

{"title":"CRISPR-Cas9-driven antigen conversion of clinically relevant blood group systems.","authors":"Yelena Boccacci, Nellie Dumont, Yannick Doyon, Josée Laganière","doi":"10.1093/hmg/ddaf040","DOIUrl":"https://doi.org/10.1093/hmg/ddaf040","url":null,"abstract":"<p><p>The common practice of blood transfusion entirely relies on blood donations from the population. Ensuring blood group compatibility between a donor and a recipient is paramount to prevent critical adverse reactions. Finding compatible blood can be challenging given the high diversity of blood group antigens, especially for chronically transfused patients at higher risk of alloimmunization owing to repeated exposures to foreign RBCs. In addition, due to the immunogenicity of the ABO blood group and the highly polymorphic nature of the Rhesus (Rh) system, they both remain of prime importance in transfusion medicine. Cultured red blood cells (cRBCs) may eventually provide an alternative for blood donations-at least in some circumstances. Combining cRBCs with blood group gene editing could broaden transfusion accessibility by making antigen expression compatible with rare phenotypes, thus meeting the needs of more patients. Starting from mobilized, erythroid-primed hematopoietic stem and progenitor cells (HSPCs), we used virus- and selection-free, CRISPR-Cas9-mediated knockouts to produce erythroid cells devoid of AB and Rh antigen. The approach yielded almost complete conversion to O- and RhNull phenotypes, as determined by standard hemagglutination and flow cytometry analyses. Combined with robust cRBC protocols, these clinically relevant phenotypic changes could eventually expand the accessibility of blood transfusion for specific and unmet clinical needs.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual faces of itaconate and its derivatives: exploring diverse biological functions in immunity and infectious diseases.","authors":"Cecilie Poulsen, Dominic G Roy, David Olagnier","doi":"10.1093/hmg/ddae177","DOIUrl":"https://doi.org/10.1093/hmg/ddae177","url":null,"abstract":"<p><p>The intersection of immunology and infectious diseases has been revolutionized by the emergence of immunometabolism, highlighting the critical role of metabolic processes in regulating immune responses. In recent years, itaconate alongside its derivatives dimethyl-itaconate (DMI) and 4-octyl-itaconate (4-OI), have received attention for their potent immunomodulatory and antimicrobial properties. This review examines the unique roles of itaconate and its derivatives in modulating immune functions and their implications in infectious diseases. We also explore their structural and functional discrepancies. Notably, while itaconate generally exhibits anti-inflammatory and antimicrobial effects, its derivatives may operate through distinct mechanisms, often exhibiting enhanced electrophilic properties. This review of recent research underscores the potential of itaconate and its derivatives as therapeutic agents, paving the way for future clinical applications in managing inflammation and infectious diseases.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare and common genetic variants underlying the risk of Hirschsprung's disease.","authors":"Jun Xiao, Chenzhao Feng, Tianqi Zhu, Xuan Zhang, Xuyong Chen, Zejian Li, Jingyi You, Qiong Wang, Didi Zhuansun, Xinyao Meng, Jing Wang, Lei Xiang, Xiaosi Yu, Bingyan Zhou, Weibing Tang, Jinfa Tou, Yi Wang, Heying Yang, Lei Yu, Yuanmei Liu, Xuewu Jiang, Hongxia Ren, Mei Yu, Qi Chen, Qiang Yin, Xiang Liu, Zhilin Xu, Dianming Wu, Donghai Yu, Xiaojuan Wu, Jixin Yang, Bo Xiong, Feng Chen, Xingjie Hao, Jiexiong Feng","doi":"10.1093/hmg/ddae205","DOIUrl":"10.1093/hmg/ddae205","url":null,"abstract":"<p><p>Hirschsprung's disease (HSCR) is a congenital enteric neuropathic disorder characterized by high heritability (>80%) and polygenic inheritance (>20 genes). The previous genome-wide association studies (GWAS) identified several common variants associated with HSCR and demonstrated increased predictive performance for HSCR risk in Europeans using a genetic risk score, there remains a notable gap in knowledge regarding Chinese populations. We conducted whole exome sequencing in a HSCR case cohort in Chinese. By using the common controls (505 controls from 1KG EAS and 10 588 controls from ChinaMAP), we conducted GWAS for the common variants in the exome and gene-based association for rare variants. We further validated the associated variants and genes in replicated samples and in vitro and vivo experiments. We identified one novel gene PLK5 by GWAS and suggested 45 novel putative genes based the gene-based test. By using genetic variant at RET and PLK5, we constructed a genetic risk score that could identify the individuals with very high genetic risk for HSCR. Compared with patients with zero or one risk allele from the three variants, the risk for HSCR was 36.61 times higher with six alleles. In addition, we delineated a HSCR risk gene landscape that encompasses 57 genes, which explains 88.5% and 54.5% of HSCR in Chinese and European, respectively. In summary, this study improved the understanding of genetic architecture of HSCR and provided a risk prediction approach for HSCR in the Chinese.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"586-598"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deregulated ion channels contribute to RHOBTB2-associated developmental and epileptic encephalopathy.","authors":"Franziska Langhammer, Anne Gregor, Niels R Ntamati, Arif B Ekici, Beate Winner, Thomas Nevian, Christiane Zweier","doi":"10.1093/hmg/ddae183","DOIUrl":"10.1093/hmg/ddae183","url":null,"abstract":"<p><p>While de novo missense variants in the BTB domains of atypical RhoGTPase RHOBTB2 cause a severe developmental and epileptic encephalopathy, de novo missense variants in the GTPase domain or bi-allelic truncating variants are associated with more variable neurodevelopmental and seizure phenotypes. Apart from the observation of RHOBTB2 abundance resulting from BTB-domain variants and increased seizure susceptibility in Drosophila overexpressing RhoBTB, our knowledge on RHOBTB2-related pathomechanisms is limited. We now found enrichment for ion channels among the differentially expressed genes from RNA-Seq on fly heads overexpressing RhoBTB. Subsequent genetic interaction experiments confirmed a functional link between RhoBTB and paralytic, the orthologue of human sodium channels, including epilepsy associated SCN1A, in vivo. We then performed patch-clamp recordings on mature neurons differentiated from human induced pluripotent stem cells with either homozygous frameshifts or patient-specific heterozygous missense variants in the GTPase or the BTB domains. This revealed significantly altered neuronal activity and excitability resulting from BTB domain variants but not from GTPase domain variants or upon complete loss of RHOBTB2. Our study indicates a role of deregulated ion channels in the pathogenesis of RHOBTB2-related developmental and epileptic encephalopathy and points to specific pathomechanisms underlying the observed genotype-phenotype correlations regarding variant zygosity, location and nature.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"639-650"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of urinary cadmium levels in current smokers from the multiethnic cohort study.","authors":"Shannon M Sullivan, Sharon E Murphy, Daniel O Stram, Lynne R Wilkens, Christopher A Haiman, Loïc Le Marchand, Irina Stepanov, S Lani Park","doi":"10.1093/hmg/ddae202","DOIUrl":"10.1093/hmg/ddae202","url":null,"abstract":"<p><strong>Background: </strong>Cadmium (Cd), classified as an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, is present in cigarette smoke. Recent studies have illustrated the potential role of genetics in influencing Cd biomarker levels.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) of urinary Cd levels in 1977 current smokers from the Multiethnic Cohort Study, comprising participants from five different racial and ethnic groups. Linear regression models were adjusted for age at urine collection, sex, self-reported race/ethnicity, and the top ten leading principal components.</p><p><strong>Results: </strong>Among the 11 710 497 single nucleotide polymorphisms (SNP) analyzed, no associations with urinary Cd reached genome-wide significance (P < 5.0 × 10-8). Notably, five variants demonstrated suggestive associations with urinary Cd levels (P < 1.0 × 10-6). Lead variants included: rs10097646 in the SCARA gene at 8q13.2 (P = 2.62 × 10-7); rs7444817 in the NIPBL gene at 5p13.2 (P = 3.10 × 10-7), rs830422 in the SPINK4 gene at 9q13.2 (P = 4.89 × 10-7); chrX:145489901 in the SLC9A7 gene at Xq121.1 (P = 5.38 × 10-7); and rs73074456 at 5p13.3 (P = 5.86 × 10-7).</p><p><strong>Conclusions: </strong>Our GWAS of urinary Cd levels in a diverse population of people who smoke, revealed suggestive associations with variants in SCARA5, NIPBL, SPINK4, SLC9A7, and 5p13.3. These findings underscore the potential role of genetic factors in understanding and mitigating the health risks associated with internal dose of carcinogens, particularly in the context of tobacco-related carcinogens.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"611-616"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression variation of long noncoding RNAs in dopaminergic cells-derived from stem cells and their MPP+ induced PD models.","authors":"Setareh Behrouzi Abady Pamsary, Fariba Esmaeili, Fariba Dehghanian, Mohammad Hadi Bahadori","doi":"10.1093/hmg/ddae192","DOIUrl":"10.1093/hmg/ddae192","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons (DA) which can be caused by environmental and genetic factors. lncRNAs have emerged as an important regulatory layer in neurodegenerative disorders, including PD. In this study, we investigated and validated lncRNAs that may serve as diagnostic or therapeutic targets for PD. Key genes associated with midbrain and DA cells were screened by differential gene expression analysis on GSE213100 dataset and candidate lncRNAs were selected for further examination. P19 cells were differentiated into DA cells and received treatment with MPP+ to induce PD-like cytotoxic events, which were confirmed by light microscopy, RT-qPCR, immunofluorescence and flow cytometry. Then, the cells were used to investigate the changes of lncRNAs Malat1, Norad, Snhg1 and Meg3. Here we found that the neuronal phenotype was mainly observed on the 12th day of differentiation and the number of DA markers significantly decreased in PD model cells compared with the control group. Moreover, the expression levels of Meg3, Norad, and Snhg1 were decreased by MPP+ whereas Malat1 level was noticeably higher in MPP+ cells compared to DA cells and the control group. In conclusion, the expression level of lncRNAs was able to show a significant difference between differentiated dopaminergic cells and their Parkinsonian model, thereby improving our understanding of the molecular pathogenesis of PD.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"599-610"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease.","authors":"Eun-Young Choi, John H Wolfe, Stephen G Kaler","doi":"10.1093/hmg/ddae201","DOIUrl":"10.1093/hmg/ddae201","url":null,"abstract":"<p><p>The choroid plexuses (CP) are highly vascularized structures that project into the ventricles of the vertebrate brain. The polarized epithelia of the CP produce cerebrospinal fluid by transporting water and ions into the ventricles from the blood and normally secrete a large number of proteins. We assessed the feasibility of selective CP transduction with recombinant adeno-associated virus (rAAV) gene therapy vectors for treatment of lysosomal storage disease (LSD), a broad category of neurometabolic illness associated with significant burdens to affected patients and their families. There are no ideal or complete therapeutic options currently available, especially for the central nervous system manifestations of LSDs. Alpha-mannosidosis (AMD) is an autosomal recessive prototypical LSD caused by deficiency of lysosomal alpha-mannosidase and characterized by cerebellar ataxia, neurocognitive disability, facial and skeletal abnormalities, hearing impairment, and mild immune deficiency. In a murine model of AMD, we compared the biochemical effects of CSF-directed rAAV serotypes 1, 4, 5, 6, and 9. Recombinant AAV1 and rAAV6, two closely related serotypes whose capsid sequences differ by only six amino acids, showed the most robust transduction of CP in mouse brain, consistent with their transduction of CPE in nonhuman primates and cats, as well as in other structures. We found restoration of LAMAN enzyme activity comparable to or higher than AMD heterozygote levels in the brain globally (olfactory bulb, cortex, cerebellum, brainstem). Further IND-generating preclinical experiments will advance rAAV6-LAMAN, which appears to be the most promising choroid plexus-targeting candidate serotype for future clinical translation to treat AMD.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"577-585"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans.","authors":"Dagne Daskeviciute, Louise Chappell-Maor, Becky Sainty, Philippe Arnaud, Isabel Iglesias-Platas, Carlos Simon, Hiroaki Okae, Takahiro Arima, Rita Vassena, Jon Lartey, David Monk","doi":"10.1093/hmg/ddaf009","DOIUrl":"10.1093/hmg/ddaf009","url":null,"abstract":"<p><p>Genomic imprinting is the parent-of-origin dependent monoallelic expression of genes often associated with regions of germline-derived DNA methylation that are maintained as differentially methylated regions (gDMRs) in somatic tissues. This form of epigenetic regulation is highly conserved in mammals and is thought to have co-evolved with placentation. Tissue-specific gDMRs have been identified in human placenta, suggesting that species-specific imprinting dependent on unorthodox epigenetic establishment or maintenance may be more widespread than previously anticipated. Non-canonical imprinting, reliant on differential allelic H3K27me3 enrichment, has been reported in mouse and rat pre-implantation embryos, often overlapping long terminal repeat (LTR)-derived promoters. These non-canonical imprints lose parental allele-specific H3K27me3 specificity, subsequently gaining DNA methylation on the same allele in extra-embryonic tissues resulting in placenta-specific, somatically acquired maternal DMRs. To determine if similar non-canonical imprinting is present in the human placenta, we interrogated allelic DNA methylation for a selected number of loci, including (i) the human orthologues of non-canonical imprinted regions in mouse and rat, (ii) promoters of human LTR-derived transcripts, and (iii) CpG islands with intermediate placenta-specific methylation that are unmethylated in gametes and pre-implantation embryos. We failed to identify any non-canonical imprints in the human placenta whole villi samples. Furthermore, the assayed genes were shown to be biallelically expressed in human pre-implantation embryos, indicating they are not imprinted at earlier time points. Together, our work reiterates the continued evolution of placenta-specific imprinting in mammals, which we suggest is linked to epigenetic differences during the maternal-to-embryo transition and species-specific integration of retrotransposable elements.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"626-638"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.","authors":"Anna Prizment, Abby Standafer, Conghui Qu, Kathleen M Beutel, Shuo Wang, Wen-Yi Huang, Annika Lindblom, Rachel Pearlman, Bethany Van Guelpen, Alicja Wolk, Daniel D Buchanan, Robert C Grant, Stephanie L Schmit, Elizabeth A Platz, Corinne E Joshu, David J Couper, Ulrike Peters, Timothy K Starr, Patricia Scott, Nathan Pankratz","doi":"10.1093/hmg/ddaf007","DOIUrl":"10.1093/hmg/ddaf007","url":null,"abstract":"<p><strong>Background: </strong>Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.</p><p><strong>Methods: </strong>Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk. For replication, we used whole exome sequencing data from UK Biobank (UKB; 5126 cases and 20 504 controls matched 4:1 based on genetic distance, age, and sex), and extended our analyses to all other heterozygous CFTR variants annotated as CF-causing.</p><p><strong>Results: </strong>In our meta-analysis of GECCO-CORECT-CCFR-ARIC, the odds ratio (OR) for CRC risk associated with Phe508del was 1.11 (P = 0.010). In our UKB replication, the OR for CRC risk associated with Phe508del was 1.28 (P = 0.002). The sequencing data from UKB also revealed an association between the presence of any other single CF-causing variant (excluding Phe508del) and CRC risk (OR = 1.33; P = 0.030). When stratifying CFTR variants by functional class, class I variants (no protein produced) had a stronger association (OR = 1.77; p = 0.002), while class II variants (misfolding and retention of the protein in the endoplasmic reticulum) other than Phe508del (OR = 1.75; p = 0.107) had similar effect size as Phe508del, and variants in classes III-VI had non-significant ORs less than 1.0 and/or were not present in cases.</p><p><strong>Conclusions: </strong>CF-causing heterozygous variants, especially class I variants, are associated with a modest but statistically significant increased CRC risk. More research is needed to explain the biology underlying these associations.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"617-625"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory role of miR-128-2-5p in serum exosomes on COL6A2 expression and postmenopausal osteoporosis.","authors":"Liangjie Lu, Lijun Wang, Huihan Wang, Minjie Yang","doi":"10.1093/hmg/ddae147","DOIUrl":"10.1093/hmg/ddae147","url":null,"abstract":"<p><p>This study investigates the influence of miR-128-2-5p within serum-derived exosomes (Exos) on COL6A2 expression and its implications in postmenopausal osteoporosis (POMP). Utilizing bioinformatics analysis, we identified 1317 differentially expressed genes (DEGs), primarily enriched in the focal adhesion pathway-a critical regulator of osteoblast adhesion. A significant gene, COL6A2, emerged as notably downregulated in POMP, possessing potential as a diagnostic marker. Predictive analysis linked the upstream miRNA miR-128-2-5p, highly enriched in Exos, with the regulation of COL6A2. Experimentally, Exos from POMP patients demonstrated elevated miR-128-2-5p levels, which inhibited COL6A2 expression in vitro, reducing osteoblast adhesion and exacerbating osteoporotic conditions. These findings highlight the pivotal role of exosomal miR-128-2-5p in bone metabolism, suggesting a novel molecular mechanism and a potential therapeutic target in POMP.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"563-576"},"PeriodicalIF":3.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}