Global Medical Genetics最新文献

{"title":"Regulatory role and subtype analysis of m6A modifications in dermatomyositis.","authors":"Xiang Long, Yidan Hu, Rui Tu, Youxian He","doi":"10.1016/j.gmg.2026.100097","DOIUrl":"10.1016/j.gmg.2026.100097","url":null,"abstract":"<p><strong>Background: </strong>Dermatomyositis (DM) is an uncommon autoimmune disease that presents challenges due to the lack of reliable biomarkers in clinical practice. Growing evidence suggests that N6-methyladenosine (m6A) is closely associated with the pathogenesis of autoimmune diseases.</p><p><strong>Methods: </strong>Microarray gene expression matrix for GSE46239, GSE128314, and GSE142807 were downloaded from the GEO database. Random forest (RF), support vector machine (SVM), and nomogram models were developed, with their performance subsequently compared. The identification of m6A subtypes, based on differentially expressed m6A regulatory genes, was followed by the classification of gene subtypes according to the differently expressed genes between the m6A subtypes. Both classification systems were subjected to m6A scoring analysis and visualized via a Sankey diagram.</p><p><strong>Results: </strong>We retrieved 99 dermatomyositis samples and 14 healthy samples. Using an RF model, we identified five core genes-IGFBP3, ZCCHC4, HNRNPC, WTAP, and RBM15-and constructed a predictive nomogram model. Two m6A clusters were developed. Cluster A exhibited a significant increase of CD56-bright natural killer cells, immature B cells, plasmacytoid dendritic cells, regulatory T cells, and type 1 T helper cells distinct from cluster B (p < 0.05). Based on 32 significantly distinctly expressed genes between m6A subtypes (p < 0.05), we further reproduced two m6A gene subtypes. The Sankey diagram showed significant concordance among m6A scores, m6A subtypes, and m6A gene subtypes.</p><p><strong>Conclusion: </strong>m6A regulatory genes significantly influence the pathogenesis of dermatomyositis. In this work, we built a predictive nomogram model, comprehensively evaluated two classification methods, and provided new insights for patient classification.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"13 1","pages":"100097"},"PeriodicalIF":1.5,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel <i>PRKACB</i> variant associated with bilateral postaxial polydactyly and intrauterine growth restriction: A case report and literature review.","authors":"Yan Zhang, Wenlong Shen, Yaer Lv, Jue Zhao, Junjie Wu, Yang Wang, Xujun He, Xiaohua Tang","doi":"10.1016/j.gmg.2025.100085","DOIUrl":"10.1016/j.gmg.2025.100085","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the clinical features of a fetus with postaxial polydactyly caused by a <i>de novo PRKACB</i> gene variant and to perform a genetic analysis.</p><p><strong>Methods: </strong>A pregnant woman who presented to Zhejiang Provincial People's Hospital on 4 December 2024 was enrolled in this study. Fetal clinical data were collected, and genomic DNA was extracted from the fetus and both parents. Clinical whole-exome sequencing (WES) was performed on the trio (fetus and both parents). Candidate variants were identified and validated by Sanger sequencing, followed by bioinformatics analysis. This study was approved by the Medical Ethics Committee of Zhejiang Provincial People's Hospital (approval number: QT2025076).</p><p><strong>Results: </strong>Prenatal ultrasonography revealed bilateral postaxial polydactyly and several fetal biometric measurements that were inconsistent with gestational age. The clinical diagnoses were intrauterine growth restriction and polydactyly. WES identified a <i>de novo</i> heterozygous variant (c.802 G>A; p.Asp268Asn) in exon 8 of the fetal <i>PRKACB</i> gene (NM_182948.4). According to the ACMG variant-classification guidelines, this variant was interpreted as likely pathogenic (PS2_Moderate, PM1, PM2_Supporting and PP3). AlphaFold-based structural prediction indicated that the PRKACB p.Asp268Asn substitution resulted in the loss of two hydrogen bonds, thereby altering the protein's three-dimensional conformation and affecting structural stability.</p><p><strong>Conclusion: </strong>The <i>PRKACB</i> gene c.802 G>A (p.Asp268Asn) variant is a potential genetic cause of bilateral postaxial polydactyly in the fetus. Identification of this variant expands the known mutational spectrum of <i>PRKACB</i> gene and provides an important reference for genetic counselling and prenatal diagnosis.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100085"},"PeriodicalIF":1.5,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12756693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic susceptibility of <i>IKZF1</i>, <i>ARID5B</i>, and <i>CEBPE</i> polymorphisms to childhood acute lymphoblastic leukemia in Chinese populations: a case-control study.","authors":"Xiaoqing Cao, Yong Wang, Yurou Kang, Muhammad Usman Abubakar, Yanli Yang, Daihua Fang, Bangshun He","doi":"10.1016/j.gmg.2025.100084","DOIUrl":"10.1016/j.gmg.2025.100084","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in <i>IKZF1</i>, <i>ARID5B</i>, and <i>CEBPE</i> with acute lymphoblastic leukemia (ALL) susceptibility in Chinese children.</p><p><strong>Methods: </strong>A case-control study was conducted involving 360 ALL patients and 398 healthy controls. Nine SNPs were genotyped, and their associations with ALL risk were analyzed using logistic regression under various genetic models. Multifactor dimensionality reduction (MDR) analysis was employed to investigate SNP-SNP interactions.</p><p><strong>Results: </strong>Seven of the nine SNPs were significantly associated with ALL susceptibility. Specifically, <i>IKZF1</i> SNPs (rs11980379, rs4132601, rs10272724) and a <i>CEBPE</i> SNP (rs4982731) were associated with an increased risk of ALL. In contrast, <i>ARID5B</i> SNPs (rs10994982, rs10821938) and another <i>CEBPE</i> SNP (rs2144827) were associated with a reduced risk. Stratified analyses revealed age- and sex-specific associations. MDR analysis identified significant SNP-SNP interactions, with a robust four-SNP model (rs10994982, rs2144827, rs10272724, rs10821938) showing the best predictive performance for ALL risk.</p><p><strong>Conclusion: </strong>Specific SNPs in <i>IKZF1</i>, <i>ARID5B</i>, <i>CEBPE</i> and their interactions are associated with childhood ALL susceptibility in Chinese populations, providing references for ALL risk stratification.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100084"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent toe walking as a prominent feature in pediatric PMP22- Related neuropathies: A retrospective cohort study.","authors":"David Pomarino, Kevin M Rostásy, Bastian Fregien, Jan Oliver Schönfeldt, Alexander Nazarkin","doi":"10.1016/j.gmg.2025.100082","DOIUrl":"10.1016/j.gmg.2025.100082","url":null,"abstract":"<p><strong>Purpose: </strong>Persistent toe walking in children is often considered idiopathic; however, increasing evidence suggests that alterations in the PMP22 gene-implicated in Charcot-Marie-Tooth disease type 1 A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)-may contribute to its pathogenesis. This study investigates the association between PMP22 variants (duplications, deletions, and point mutations) and toe walking in children, aiming to delineate their clinical and genetic characteristics.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 22 pediatric patients (mean age: 7.7 years) with persistent toe walking and confirmed PMP22 variants identified through a 49-gene next-generation sequencing (NGS) panel. In selected cases, Multiplex Ligation-dependent Probe Amplification (MLPA) was applied to confirm copy number variations. Comprehensive clinical evaluations included musculoskeletal, neurological, and developmental assessments.</p><p><strong>Results: </strong>All identified variants demonstrated dominant inheritance. Pathogenic variants were present in 54.5 % of patients, likely pathogenic in 31.8 %, and variants of uncertain significance (VUS) in 13.6 %. Among pathogenic cases, most carried PMP22 duplications, one had a deletion, and the remainder harbored the missense variant p.(Thr118Met). The three VUS carriers exhibited comparatively milder phenotypes, such as muscle cramps, lumbar hyperlordosis, mild dorsiflexion restriction, hyporeflexia, pes cavus, and clinodactyly/brachydactyly; only one presented with tremor. Lumbar hyperlordosis (90.9 %) and pes cavus (90.9 %) were the most consistent findings.</p><p><strong>Conclusions: </strong>Persistent toe walking may represent an early sign of PMP22-related neuropathies rather than a benign idiopathic gait pattern. The predominance of PMP22 duplications and characteristic neuromuscular features highlight the clinical utility of integrating NGS and MLPA testing for accurate diagnosis, targeted management, and genetic counseling.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100082"},"PeriodicalIF":1.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation.","authors":"Xiao-Yue Tang, Jia-Huan Chen, Ran Yang, Hong Fan, Ke Yang, Tao Ding, Qiao-Chu Wang, Ye-Hong Yang, Yue Wu, Zhi-Yi Zhang, Chun-Mei Shi, Xue-Hui Liu, Jiang-Feng Liu, Xiang Lv, Jun-Tao Yang","doi":"10.1016/j.gmg.2025.100083","DOIUrl":"10.1016/j.gmg.2025.100083","url":null,"abstract":"<p><strong>Background: </strong>Terminal erythroid differentiation (TED) is the maturation process of proerythroblasts into enucleated erythrocytes. Animal models are essential for studying red blood cell disorders.</p><p><strong>Methods: </strong>We isolated erythroblasts at different TED stages from mouse bone marrow using FACS and performed integrated multi-omics analyses.</p><p><strong>Results: </strong>We developed a stage-specific transcriptome and proteome profile, enhancing murine TED databases. The most significant changes occurred during the transition from proerythroblasts to basophilic erythroblasts, characterized by immune function suppression and activation of erythroid processes. Global gene and protein expression dynamics showed that orthochromatic erythroblasts exit the cell cycle, with transcription cofactors histone deacetylase 1(HDAC1), histone deacetylase 2(HDAC2), and cell division control protein 6 homolog (CDC6), playing key roles in cell cycle regulation. Additionally, autophagy was initiated at the basophilic stage, indicated by increased autophagy-related gene (ATG) mRNA levels and activation of autophagy marker proteins like microtubule associated protein 1 light chain 3 beta (LC3-I), optineurin (OPTN), and ATGs, including Atg7, Atg4b, Atg3, and Atg2b.</p><p><strong>Conclusions: </strong>Overall, we have generated a foundational murine transcriptome and proteome dataset, providing insights into the functional dynamics and regulatory mechanisms of terminal erythroid differentiation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100083"},"PeriodicalIF":1.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of IL-6 and IL-1β Gene coding and study on specific clearance using histidine-grafted PVDF membranes.","authors":"Ke Li, JuanJuan Liu, Kuo Zhang, Hui Liu, Yi Yang, Ren Na, Hui Ma, XiaoJian Cui","doi":"10.1016/j.gmg.2025.100080","DOIUrl":"10.1016/j.gmg.2025.100080","url":null,"abstract":"<p><p>Severely infected patients produce large amounts of inflammatory cytokines, such as interleukin-6 (IL-6) and interleukin-1β (IL-1β), leading to a \"cytokine storm\", which is a clinically refractory condition. Because IL-6 and IL-1β differ significantly in gene family, chromosomal location, protein structure, and signaling pathways, existing techniques are ineffective at simultaneously removing cytokines. This work developed a novel blood purification material by chemically grafting histidine onto a polyvinylidene fluoride (PVDF) membrane. ATR-FTIR and XPS analyses confirmed the successful grafting of histidine onto the PVDF membrane. Following histidine grafting, the membrane's adsorption capacity for IL-6 in aqueous solution increased with histidine concentration. The optimized histidine-grafted PVDF membrane achieved adsorption rates of (36 ± 4)% for IL-6 and (63 ± 5) % for IL-1β in plasma. Additionally, the histidine-grafted PVDF membrane demonstrated enhanced biocompatibility, exhibiting a low hemolysis rate, minimal adsorption of red blood cells and platelets, and anticoagulant properties without activating the coagulation cascade. This histidine-grafted PVDF membrane offers a promising new therapeutic strategy for treating severe infections and holds significant potential for clinical application.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100080"},"PeriodicalIF":1.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting non-coding RNAs to overcome resistance and improving outcomes in glioblastoma.","authors":"Dhruv Parikh, Manan Shah","doi":"10.1016/j.gmg.2025.100075","DOIUrl":"10.1016/j.gmg.2025.100075","url":null,"abstract":"<p><p>Glioblastoma (GB) remains the most aggressive and treatment-resistant primary brain tumor, characterized by extensive heterogeneity, therapeutic resistance, and dismal prognosis. In this comprehensive review, we aimed to synthesize emerging insights into the roles of non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, circular RNAs, and PIWI-interacting RNAs-in the regulation of glioblastoma progression, resistance mechanisms, and potential therapeutic strategies. We critically evaluated the molecular functions of ncRNAs in key oncogenic processes such as proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and immune evasion. Additionally, we reviewed current detection methods, delivery technologies, and clinical trials targeting these ncRNAs. A central goal of this review was to bridge a notable gap in the literature by highlighting underrepresented ncRNA classes such as circRNAs and piRNAs, which exhibit regulatory complexity and potential as biomarkers and therapeutic agents in GB. We further discussed delivery challenges posed by the blood-brain barrier and explored promising nanocarrier and exosome-based approaches to enhance therapeutic targeting. Through curated case studies, we showcased the translational potential of targeting specific ncRNAs to reverse multiple resistance types and improve immunotherapy response. This review provides a consolidated framework for understanding the dynamic role of ncRNAs in glioblastoma and proposes an expanded toolkit for precision oncology approaches. Our findings not only underscore the therapeutic promise of ncRNAs but also call for future investigations into the lesser-known subclasses that could redefine the landscape of GB management.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"12 4","pages":"100075"},"PeriodicalIF":1.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12731266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Plasminogen Activator Inhibitor 1 ( <i>PAI1</i> ) in Ovarian Cancer: Mechanisms and Therapeutic Implications.","authors":"Sneha Grace Mathews, R B Devi Krishna, Lavanya M, Nandini K, Sanjana Murali, Preet Agarwal, Elizabeth Rani, Andrea Mary F","doi":"10.1055/s-0044-1791734","DOIUrl":"10.1055/s-0044-1791734","url":null,"abstract":"<p><p>Ovarian cancer (OC) is one among most significantly fatal gynecological cancers, with late-stage detection and an inadequate prognosis. Plasminogen activator inhibitor-1 ( <i>PAI1</i> ) gene anticipates negative outcomes in many different kinds of malignancies. Several research investigations are currently being done to examine the biological role of <i>PAI1</i> in OC and the possible benefits of targeted pharmacotherapies. The <i>PAI1</i> gene has been linked to the emergence and development of cancer in the ovary. <i>PAI1</i> , an inhibitor of serine protease, influences the fibrinolysis and extracellular matrix remodeling, both of which are crucial for tumor expansion and metastatic growth. <i>PAI1</i> levels have been discovered to be subsequently more elevated in malignant ovarian tissues than in usual ovarian tissue, demonstrating a potential connection among <i>PAI1</i> overexpression and OC development. <i>PAI1</i> promotes tumor cell proliferation, movement, and an invasion by influencing the urokinase-plasminogen activators and through interactions with cell surface receptors. In addition, <i>PAI1</i> gene contributes to angiogenesis and apoptotic cell death, which contribute to the more hostile phenotypes of OC. The prognostic and therapeutic consequences of focusing on <i>PAI1</i> in OC are explored, demonstrating <i>PAI1</i> 's potential to be a biomarker and emphasizing for novel treatment approaches. The <i>PAI1</i> gene possesses several functions in OC, affecting tumor development, an invasion, and metastatic growth. Comprehending the complicated interactions and mechanisms that regulate <i>PAI1</i> in OC may lead to more efficient evaluation and treatment strategies and ultimately enhance patient outcomes.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"358-365"},"PeriodicalIF":1.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of CRISPR/Cas9 in Revolutionizing Duchenne's Muscular Dystrophy Treatment: Opportunities and Obstacles.","authors":"Ahsan Ali, Md Yakeen Rahman, Danish Sheikh","doi":"10.1055/s-0044-1791803","DOIUrl":"10.1055/s-0044-1791803","url":null,"abstract":"<p><p>Duchenne's muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration, leading to loss of ambulation, respiratory failure, and premature death. It affects approximately 1 in 3,500 live male births and is caused by mutations in the dystrophin gene, which impairs muscle fiber stability. Current treatments are limited to managing symptoms and slowing disease progression, with no curative therapies available. The advent of CRISPR/Cas9 gene-editing technology has introduced a promising approach for directly correcting the genetic mutations responsible for DMD. This review explores the potential of CRISPR/Cas9 as a transformative therapy for DMD, highlighting its successes in preclinical models, the challenges associated with its delivery, and the obstacles to its clinical application. While preclinical studies demonstrate the efficacy of CRISPR/Cas9 in restoring dystrophin expression and improving muscle function, significant hurdles remain, including optimizing delivery methods and ensuring long-term safety.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"349-357"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Alpha6 Integrin Disorder Presenting in Childhood with Nail Dysplasia and Onycholysis But No History of Fragile or Bullous Skin Changes.","authors":"Alayna N Zalesny, Sarah Gunter, Charles A Williams","doi":"10.1055/s-0044-1791804","DOIUrl":"10.1055/s-0044-1791804","url":null,"abstract":"<p><p>We report a 7-year-old girl born with pyloric atresia but without congenital epidermolysis bullosa or skin fragility. Nail dysplasia developed at age 8 months and throughout childhood she suffered from onycholysis and mild nail hypertrophy. Whole-exome sequencing demonstrated biallelic mutations in alpha6 integrin (ITGA6): p. Q139* and R153W. ITGA6 normally forms a protein heterodimer with beta4 integrin (ITGB4), and this dimer participates in anchoring the basal skin cells to the extracellular matrix. Biallelic mutations in each gene are well known to cause epidermolysis bullosa and pyloric atresia. However, this child had ostensibly normal skin without any evidence of skin fragility. In a literature search, we identified 11 cases involving ITGA6 mutations, and all had epidermolysis skin changes. Thus, this case adds to the reported phenotype of ITGA6 disease since it is the first to show absence of an epidermolysis bullosa phenotype in the setting of pyloric atresia and nail dysplasia.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"344-348"},"PeriodicalIF":1.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}