BMC Medical Genomics最新文献

{"title":"Mendelian randomization analysis reveals higher whole body water mass may increase risk of bacterial infections.","authors":"Peng Yan, Jiahuizi Yao, Ben Ke, Xiangdong Fang","doi":"10.1186/s12920-024-01950-3","DOIUrl":"10.1186/s12920-024-01950-3","url":null,"abstract":"<p><strong>Background and purpose: </strong>The association of water loading with several infections remains unclear. Observational studies are hard to investigate definitively due to potential confounders. In this study, we employed Mendelian randomization (MR) analysis to assess the association between genetically predicted whole body water mass (BWM) and several infections.</p><p><strong>Methods: </strong>BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted.</p><p><strong>Results: </strong>Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10^- 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10^- 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10^- 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10^- 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits.</p><p><strong>Conclusions: </strong>In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"183"},"PeriodicalIF":2.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between OX40L polymorphism and type 2 diabetes mellitus in Iranians.","authors":"Abdolreza Sotoodeh Jahromi, Saiedeh Erfanian, Abazar Roustazadeh","doi":"10.1186/s12920-024-01958-9","DOIUrl":"10.1186/s12920-024-01958-9","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus (DM) is one of the leading causes of morbidity and mortality worldwide. It is a multifactorial disease that genetic and environmental factors contribute to its development. The aim of the study was to investigate the association of OX40L promoter gene polymorphisms with type 2 diabetes mellitus (T2DM) in Iranians.</p><p><strong>Materials and methods: </strong>Three hundred and sixty-eight subjects including 184 healthy subjects and 184 T2DM patients were enrolled in our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to detect genotype and allele frequencies of rs3850641, rs1234313 and rs10912580. In addition, SNPStats web tool was applied to estimate haplotype frequency and linkage disequilibrium (LD).</p><p><strong>Results: </strong>The distribution of tested polymorphisms was statistically different between the T2DM patients and healthy subjects (P < 0.01). rs1234313 AG (OR = 0.375, 95% CI = 0.193-0.727, P = 0.004) and rs10912580 AG (OR = 0.351, 95% CI = 0.162-0.758, P = 0.008) genotypes were associated with the decreased risk of T2DM in Iranians. Moreover, our prediction revealed that AAG (OR = 0.46, 95% CI= (0.28-0.76), P = 0.0028) and GAG (OR = 0.24, 95% CI= (0.13-0.45), P < 0.0001) haplotypes were related to the reduced risk of the disease. However, the tested polymorphisms had no effect on biochemical parameters and body mass index (BMI) in the patient group (P > 0.05).</p><p><strong>Conclusion: </strong>Our findings revealed that OX40L promoter gene polymorphisms are associated with T2DM. Moreover, genotype and allelic variations were related to the decreased risk of T2DM in Iranians. Further studies are recommended to show whether these polymorphic variations could affect OX40/OX40L interaction or OX40L phenotype.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"184"},"PeriodicalIF":2.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.","authors":"Duocai Wang, Meize Pan, Hang Li, Minchun Li, Ping Li, Fu Xiong, Hongbo Xiao","doi":"10.1186/s12920-024-01953-0","DOIUrl":"10.1186/s12920-024-01953-0","url":null,"abstract":"<p><strong>Background: </strong>Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient.</p><p><strong>Methods: </strong>We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R).</p><p><strong>Results: </strong>We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same.</p><p><strong>Conclusions: </strong>Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"181"},"PeriodicalIF":2.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of Ph⁺ acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?","authors":"Qi Zhang, Jing-Dong Zhou, Hao Ding, Lei Yang, Chao Lu, Ming-Qiang Chu, Jun Qian, Ting-Juan Zhang","doi":"10.1186/s12920-024-01955-y","DOIUrl":"10.1186/s12920-024-01955-y","url":null,"abstract":"<p><strong>Background: </strong>Philadelphia chromosome positive (Ph⁺) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph⁺ ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare.</p><p><strong>Case presentation: </strong>An 84-year-old man with fatigue and dizziness was diagnosed with Ph⁺ ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases.</p><p><strong>Conclusion: </strong>As far as we know, we for the first time reported a case of Ph⁺ ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"182"},"PeriodicalIF":2.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic evidence for causal association between migraine and dementia: a mendelian randomization study.","authors":"Qiuyi Chen, Chengcheng Zhang, Shiyang Wu, Yiwei He, Yuhan Liu, Libin Zheng, Bin Li, Guiyou Liu, Lu Liu","doi":"10.1186/s12920-024-01956-x","DOIUrl":"10.1186/s12920-024-01956-x","url":null,"abstract":"<p><strong>Background: </strong>There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB).</p><p><strong>Methods: </strong>Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia. Single nucleotide polymorphisms (SNPs) associated with migraine and each dementia subtype were selected. MR analysis was conducted using inverse variance weighting (IVW) and weighted median (WM) methods. Sensitivity analyses included Cochran's Q test, MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, the intercept of MR-Egger, and leave-one-out analysis.</p><p><strong>Results: </strong>Migraine showed a significant causal relationship with AD and VaD, whereas no causal relationship was observed with all-cause dementia, FTD, or DLB. Migraine may be a potential risk factor for AD (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 0.02-0.14; P = 0.007), while VaD may be a potential risk factor for migraine (OR: 1.04; 95% CI: 0.02-0.06; P = 7.760E-5). Sensitivity analyses demonstrated the robustness of our findings.</p><p><strong>Conclusion: </strong>Our study suggest that migraine may have potential causal relationships with AD and VaD. Migraine may be a risk factor for AD, and VaD may be a risk factor for migraine. Our study contributes to unraveling the comprehensive genetic associations between migraine and various types of dementia, and our findings will enhance the academic understanding of the comorbidity between migraine and dementia.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"180"},"PeriodicalIF":2.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review.","authors":"Nahid Rezaie, Nader Mansour Samaei, Ayda Ghorbani, Naghmeh Gholipour, Shohreh Vosough, Mahboobeh Rafigh, Abolfazl Amini","doi":"10.1186/s12920-024-01949-w","DOIUrl":"10.1186/s12920-024-01949-w","url":null,"abstract":"<p><strong>Background: </strong>The SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene.</p><p><strong>Methods: </strong>In this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing.</p><p><strong>Results: </strong>In our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein.</p><p><strong>Conclusion: </strong>Our study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"178"},"PeriodicalIF":2.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.","authors":"Haozheng Cheng, Yangliu Dong, Le Wang, Xian Zhao, Xiangyi Zhe, Dongmei Li, Hongtao Li, Renfu Shao, Jing Tuo, Zemin Pan","doi":"10.1186/s12920-024-01926-3","DOIUrl":"10.1186/s12920-024-01926-3","url":null,"abstract":"<p><strong>Background: </strong>There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response.</p><p><strong>Methods: </strong>HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection.</p><p><strong>Results: </strong>Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups.</p><p><strong>Conclusions: </strong>Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"179"},"PeriodicalIF":2.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A healthy live birth after mosaic blastocyst transfer in preimplantation genetic testing for GATA1-related cytopenia combined with HLA matching.","authors":"Huiling Xu, Jiajie Pu, Zhengzhong Wu, Yulong Huang, Chanlin Han, Xuemei Li","doi":"10.1186/s12920-024-01951-2","DOIUrl":"10.1186/s12920-024-01951-2","url":null,"abstract":"<p><strong>Background: </strong>GATA1-related cytopenia (GRC) is characterized by thrombocytopaenia and/or anaemia ranging from mild to severe. Haematopoietic stem cell transplantation (HSCT) is a healing therapeutic choice for GRC patients. We identified a novel pathogenic variant (GATA1: c.1019delG) in a boy with GATA1-related cytopenia. Then we performed preimplantation genetic testing (PGT) in this GRC family. After a mosaic embryo transfered, a healthy and HLA-compatible with the proband baby was delivered.</p><p><strong>Case presentation: </strong>The proband is a 6-year-old boy who was diagnosed to have transfusion-dependent anaemia since 3 year old. Whole-exome sequencing (WES) showed that the proband has a hemizygous variant c.1019delG in GATA1, which is inherited from his mother. His parents decided to undergo PGT to have a health and HLA-compatible offspring. After whole genome amplification (WGA) of biopsied trophectoderm (TE) cells, next generation sequencing (NGS)-based PGT was preformed to analyse embryos on chromosomal aneuploidy, target mutation and HLA typing. There were 3 embryos HLA-matched to the proband. The genotypes of the 3 embryos were heterozygous variant, hemizygous variant, normal respectively. After a heterozygous, mosaic partial trisomy (chr)16, and HLA-matched embryo transfer, a healthy baby was delivered and whose HSCT is compatible with the proband.</p><p><strong>Conclusions: </strong>NGS-based PGT-HLA is a valuable procedure for the treatment of GATA1-related cytopenia caused by GATA1 variants, or other haematological disorders, oncological and immunological diseases. Furthermore, our study reconfirms that mosaic embryos transfer would bring healthy offspring.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"177"},"PeriodicalIF":2.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families.","authors":"Syeda Iqra Hussain, Nazif Muhammad, Shahbaz Ali Shah, Adil U Rehman, Sher Alam Khan, Shamim Saleha, Yar Muhammad Khan, Noor Muhammad, Saadullah Khan, Naveed Wasif","doi":"10.1186/s12920-024-01943-2","DOIUrl":"10.1186/s12920-024-01943-2","url":null,"abstract":"<p><strong>Background: </strong>Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome.</p><p><strong>Methods: </strong>Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing.</p><p><strong>Results: </strong>In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family.</p><p><strong>Conclusions: </strong>The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"176"},"PeriodicalIF":2.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the OPHN1 novel variant c.1025+1 G>A on RNA splicing: insights from a minigene assay.","authors":"Fei Yang, Minghui Wang","doi":"10.1186/s12920-024-01952-1","DOIUrl":"10.1186/s12920-024-01952-1","url":null,"abstract":"<p><p>This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient's mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene's mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"175"},"PeriodicalIF":2.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}