Journal of Genetics最新文献

{"title":"Deletion of <i>RAI1</i> noncoding exons 1-2 causes Smith-Magenis syndrome.","authors":"Uri Hamiel, Alina Kurolap, Chofit Chai Gadot, Adi Mory, Anat Bar Shira, Hagit Baris Feldman, Daphna Marom","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by developmental delay and a typical behavioral phenotype. Interstitial 17p11.2 deletions, which include the RAI1 gene are detected in >90% of patients, while single nucleotide variants (SNVs) are detected in the rest. The <i>RAI1</i> gene is encoded from exons 3 onwards, while exons 1-2 are noncoding. It is unclear whether genetic variants preceding exon 3 cause SMS. We evaluated a 15-month-old infant for developmental delay and infantile spasms who was found to carry a deletion encompassing exons 1-2 of <i>RAI</i>. To determine whether the deletion of the noncoding exons 1-2 of the <i>RAI1</i> gene is associated with SMS and to elucidate the underlying mechanism of this association. A singleton exome-based gene panel was performed, followed by chromosomal-microarray (CMA) to confirm the results. Real time quantitative PCR (RT-qPCR) analysis was conducted to evaluate <i>RAI1</i> mRNA expression. CMA confirmed a de novo 737.8 kbp deletion on 17p11.2, which includes exons 1-2 of <i>RAI1</i> but spares exons 3 onwards. RT-qPCR analysis on RNA extracted from the patient, father and three unrelated controls revealed that the patient has <i>RAI1</i> haploinsufficiency. We show that deletion of the <i>RAI1</i> noncoding exons 1-2, which spares the gene's coding region, causes <i>RAI1</i> haploinsufficiency by eliminating regulatory elements, including the gene promoter, thus causing SMS and expanding the mutational spectrum of SMS.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NGLY1-CDDG: report of two cases from India and brief review of literature.","authors":"Mihika B Dave, Vrajesh P Udani, Anaita U Hegde, Tester F Ashavaid, Alpa J Dherai","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>N-glycanase1 (NGLY1) deficiency, an autosomal recessive disorder identified a decade ago, is categorized as a congenital disorder of deglycosylation (CDDG). This disorder arises from bi-allelic variants in the <i>NGLY1</i> gene, leading to impaired protein deglycosylation. Phenotypically, individuals with <i>NGLY1</i> deficiency present with intellectual disability, movement disorders, liver dysfunction, muscular hypotonia, etc., termed as NGLY1-CDDG, its diagnosis relies primarily on next generation sequencing (NGS) and till date, it has been diagnosed in over 100 patients. However, there are no previous reports on this from India. We report the first two <i>NGLY1</i> cases from India in this study. These patients presented with developmental delay, movement disorder, microcephaly, hypotonia and suspicion of congenital disorder of glycosylation (CDG) and were assessed for glycosylation defect using the high pressure liquid chromatography (HPLC) based transferrin isoform analysis and whole exome sequencing (WES). Both patients exhibited a normal transferrin isoform pattern and harboured variants in <i>NGLY1</i> gene. The variants, NM_018297.4:c.571C[T; p.Gln191Ter and NM_018297.4:c.707G[A; p.Trp236Ter on exons 4 and 5, respectively, identified in our patients are bi-allelic loss of function homozygous variants that have not been previously reported. These variants are inferred as pathogenic in view of genotype-phenotype correlation, parental segregation analysis, <i>in-silico</i> analyses, and absence of other genetic disorders. We have also summarized literature reports on NGLY1-CDDG and compared the phenotype and variants of our patients with the reported cases. These cases contribute to the clinical, biochemical, and molecular understanding of <i>NGLY1</i> deficiency among Indians, thereby elucidating the presence of NGLY1-CDDG in India.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YY1 as a mediator to enhance the resistance of KRAS mutant colorectal cancer cells to cetuximab","authors":"Yi Ma, Yue Hu, Yi Lin, Congying Wang, Yujie Lv, Wei Chen","doi":"10.1007/s12041-024-01487-5","DOIUrl":"https://doi.org/10.1007/s12041-024-01487-5","url":null,"abstract":"","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147922820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel intron variant in the prolactin gene associated with eggshell weight and thickness with putative alternative splicing patterns in chickens","authors":"Dhafer A. Ali, Nihad Abdul-Lateef Ali, Thamer R. S. Aljubouri, Mohammed Baqur S. Al-Shuhaib","doi":"10.1007/s12041-024-01482-w","DOIUrl":"https://doi.org/10.1007/s12041-024-01482-w","url":null,"abstract":"<p>Raising Iraqi indigenous chickens (IIC) is restricted by their thin and low eggshell weights. Due to the importance of the prolactin (<i>Prl</i>) gene in regulating a wide range of egg production traits, this study assessed the potential genetic polymorphisms associated with <i>Prl</i> that may influence these traits. The polymorphism was examined in three <i>Prl</i> loci of the IIC breed (<i>n</i> = 120) in comparison with the standard Hyline breed (<i>n</i> = 120). The polymorphism of both breeds was associated with eggshell weight and thickness indices for 16 weeks, starting from the 44th to the 59th week. After genotyping three loci within <i>Prl</i> by polymerase chain reaction-single-stranded conformation polymorphism (SSCP) method, only one novel SNP was identified in intron 4, namely 129G &gt; A. The identified intron SNP exerted a significant association with both eggshell thickness and weight indices throughout the investigation period. Birds with GG genotype exhibited higher indices of eggshell thickness and weight than those with the GA and AA genotypes, respectively. The employed <i>in silico</i> tools predicted a remarkable ability for the identified SNP to alter the mRNA splicing pattern, which might be related to altered prolactin activity in birds having an alternative allele A. This study is the first to suggest the significance of this novel intron SNP in assessing eggshell traits in chickens.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"86 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the contribution of VDR and VDBP/GC genes in the pathogenesis of celiac disease","authors":"Pratibha Banerjee, Harinder Singh, Priyanka Tiwari, Ajit Sood, Vandana Midha, Gursewak Singh, B K Thelma, Sabyasachi Senapati","doi":"10.1007/s12041-024-01480-y","DOIUrl":"https://doi.org/10.1007/s12041-024-01480-y","url":null,"abstract":"<p>Vitamin-D deficiency (VDD) is a global health concern. It is known to play a critical role in the immunomodulation, and thus, its metabolism could be investigated to unravel its contribution in common immune-mediated diseases, e.g., celiac disease (CD). Genotyping of SNPs from vitamin D receptor (<i>VDR</i>) gene, such as rs11568820 (Cdx2) and rs2228570 (Fok1) using allele specific multiplex polymerase chain reaction (ASM-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively; and rs7041 and rs4588 of vitamin D binding protein (<i>VDBP/GC</i>) using PCR-RFLP were done in 969 subjects including CD cases (<i>n</i>=506) and controls (<i>n</i>=463). Genotype data for 86 CD and 712 controls for rs11568820 and rs7041 were retrieved from already published Immunochip genotype data. Serum concentration of vitamin-D and vitamin D binding protein (VDBP) were measured for 283 participants (98 CD and 185 controls). rs4588-A allele was identified as protective allele [OR=0.6(0.4–0.7), <i>P</i>&lt;0.0001]. Significantly reduced serum level of vitamin-D was observed in CD patients [median=16.25 ng/mL, IQR (8.94–23.60)] than in controls [median=19.94 ng/mL, IQR (13.91–28.46)] with <i>P</i>=0.001. Notably, rs7041-GG, rs4588-CC, and 1F (GC) haplotype of <i>VDBP</i>/<i>GC</i> showed significant association (<i>P</i>&lt;0.05) with reduced serum vitamin D level. We did not find any significant association with VDBP serum concentration. Significant vitamin D and VDBP level correlations were observed in controls (spearman r = 0.3, <i>P</i>=0.005). The present study highlights the significance of reduced vitamin-D serum level in CD. 1F variant of <i>VDBP</i> and lower vitamin-D levels contribute to CD. No correlation between vitamin-D and VDBP levels suggests that vitamin-D supplementation may improve vitamin-D levels but might not affect VDBP levels in CD subjects.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"42 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel missense variant in PNLDC1 associated with nonobstructive azoospermia","authors":"Mouness Rahimian, Masomeh Askari, Najmeh Salehi, Mojtaba Jaafarinia, Mohsen Forouzanfar, Navid Almadani, Andrea Riccio, Mehdi Totonchi","doi":"10.1007/s12041-024-01478-6","DOIUrl":"https://doi.org/10.1007/s12041-024-01478-6","url":null,"abstract":"<p>The most severe type of male infertility is nonobstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis. The predictable frequency of NOA in the general population is one in 100 men. Genetic studies have recognized dozens of NOA genes. Most NOA aetiologies remain idiopathic. Monogenic mutations can be a reason for a part of idiopathic NOA cases. To address this, we studied the pedigree of a consanguineous family with three NOAs by a family-based exome sequencing. Our goal was to pinpoint the genetic variants responsible for idiopathic NOA to aid future clinical genetic diagnostics and treatment strategies. Bioinformatics analysis followed by Sanger sequencing revealed that NOA patients were homozygous for a rare novel missense variant in <i>PNLDC1</i> (NM_173516:exon9:c.710G&gt;A;p.Gly237Asp). <i>In silico,</i> single-cell RNA sequencing data analysis and protein modelling demonstrated that PNLDC1, Gly237Asp resided in the conserved region of the CAF1 domain which could lead to local instability in the structure and alteration of protein phosphorylation site. We conclude that the novel missense <i>PNLDC1</i> variant may affect meiosis and spermatogenesis, leading to NOA and the genetic cause of this idiopathic NOA family. Our result helps genetic counselling for idiopathic NOA cases and provides the occasion for more efficient diagnosis in the clinical setting.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"25 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-7160 inhibits gastric cancer cell proliferation and metastasis by silencing SIX1","authors":"Meng Meng, Guoxin Guan, Xingming Liu, Wei Sun, Xinye Cui, Saiya Fu, Fuwen Luo","doi":"10.1007/s12041-024-01479-5","DOIUrl":"https://doi.org/10.1007/s12041-024-01479-5","url":null,"abstract":"<p>Upregulation of homeoprotein <i>SIX1</i> in gastric cancer (GC) is related to tumour proliferation and invasion. MicroRNA-7160 (miR-7160) is a homeoprotein <i>SIX1</i>-targeting miRNA that downregulates miR-7160, leading to cancer development. Total gastric cancer samples were collected from six patients, and relative expression levels of <i>SIX1</i> mRNA and miRNAs were analysed by qRT-PCR. To evaluate the regulation of <i>SIX1</i> by miR-7160, pGL3-SIX1-mut, pGL3-SIX1, and miR-7160 mimics transfected into cells using lipofectamine 2000. After transfection, proliferation and apoptosis in cultured cells were assessed using the nuclear TUNEL staining and CCK8 reagent, respectively. We demonstrated that the downregulation of miR-7160 in human gastric cancer cells is related to the upregulation of <i>SIX1</i> mRNA. In gastric cancer cell lines, miR-7160 overexpression could downregulate the expression and inhibit cancer cell proliferation and growth <i>in vitro</i>. However, overexpression of miR-7160 did not increase gastric cancer cell apoptosis. <i>In vitro</i> downregulation of <i>SIX1</i> decreased vimentin, N-cadherin, and other EMT-related gene expression and increased E-cadherin expression. In brief, miR-7160, by targeting <i>SIX1</i>, inhibits gastric cancer proliferation and cell growth <i>in vitro</i>, which provides an idea for introducing a new treatment option for gastric cancer.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"42 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COQ7 splice site variant causing a spastic paraparesis phenotype in siblings","authors":"Haseena Sait, Manmohan Pandey, Shubha R. Phadke","doi":"10.1007/s12041-024-01477-7","DOIUrl":"https://doi.org/10.1007/s12041-024-01477-7","url":null,"abstract":"<p>The <i>COQ7</i> gene is one of the causative genes for primary COQ10 deficiency-related disorders. OMIM-related phenotypes include severe encephalo-myo-nephrocardiopathy and distal hereditary motor neuronopathy. In the present study, we performed the exome sequencing analysis on the proband of a single family with two siblings affected by hereditary spastic paraparesis (HSP). Segregation analysis was conducted on the affected siblings and parents using the Sanger sequencing. <i>In silico</i> secondary and tertiary pre-mRNA structure analysis and protein modelling were carried out. Exome sequencing identified a homozygous splice site variant in the <i>COQ7</i> gene (NM_016138.5: c.367+5G&gt;A) in the proband. Sanger sequencing confirmed the homozygous status in the affected sibling and heterozygous status in both parents, consistent with autosomal recessive inheritance. <i>In silico</i> secondary and tertiary premRNA structure analysis and protein modelling predicted the deleterious nature of the variant. This case highlights a distinct intermediate phenotype of <i>COQ7</i> related disorders comprising early-onset spastic paraparesis due to a novel splice site variant in the <i>COQ7</i> gene. This expands the spectrum of clinical manifestations associated with <i>COQ7</i> deficiency and underscores the importance of considering <i>COQ7</i> gene mutations in the differential diagnosis of HSP.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"153 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141587456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the genetic and phenotypic spectrum of Baker–Gordon syndrome: a new de novo SYT1 variant","authors":"Francisco Javier Cotrina-Vinagre, María Elena Rodríguez-García, Lucía Del Pozo-Filíu, Pilar Quijada-Fraile, Francisco Martínez-Azorín","doi":"10.1007/s12041-024-01476-8","DOIUrl":"https://doi.org/10.1007/s12041-024-01476-8","url":null,"abstract":"<p>We report the case of a Spanish pediatric patient with developmental delay, hypotonia, feeding difficulties, visual problems, and hyperkinetic movements. Whole-exome sequencing uncovered a new heterozygous <i>de novo</i> Synaptotagmin 1 (<i>SYT1</i>) missense variant, NM_005639.3:c.930T&gt;A (p.Asp310Glu), in a female proband. This gene encodes the synaptotagmin-1 (SYT1) protein, which is a component of a protein complex involved in the fusion of synaptic vesicles with the presynaptic membrane. Pathogenic <i>SYT1</i> variants have been associated with Baker–Gordon syndrome (BAGOS), an autosomal dominant neurodevelopmental disorder. Although up to 30 cases have been identified worldwide, to the best of our knowledge, this is the first patient described with mitochondrial respiratory chain deficiencies and rod–cone dysfunction. In conclusion, our data expand both the genetic and phenotypic spectrum associated with <i>SYT1</i> variants.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"4 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of caudal type homeobox 1 (CDX1) gene methylated DNA, as a stool-based diagnostic biomarker in colorectal cancer","authors":"Sarina Almasi, Lida Haghnazari, Seyedeh Ozra Hosseini, Nayebali Rezvani","doi":"10.1007/s12041-024-01473-x","DOIUrl":"https://doi.org/10.1007/s12041-024-01473-x","url":null,"abstract":"<p>Colorectal cancer (CRC) is known to develop due to the accumulation of both genetic and epigenetic alterations, resulting in the conversion of intestinal epithelial cells to malignant adenocarcinoma cells. Caudal type homeobox 1 (<i>CDX1</i>) gene is a homeobox transcription factor and a selective tumour suppressor gene that is an important factor for the development of intestinal cells. This gene plays a role in the differentiation of intestinal epithelial cells, and its expression decreases in a number of cell lines derived from CRC, which suggests that a lack of <i>CDX1</i> expression is a risk factor for the development of colorectal carcinoma. Therefore, the methylated DNA amounts of <i>CDX1</i> gene in stool samples were investigated as a noninvasive method for the detection of CRC. In the present study, the methylation of <i>CDX1</i> gene promoter region was assessed in stool samples of 50 CRC patients and 50 healthy individuals by MethyLight PCR using two primers and a Taq Man probe, which was completely specifically designed for fully methylated DNA of the gene promoter region. The percentage of methylated reference (PMR) of the studied gene in all samples was calculated similarly to previous studies. Statistical analysis was performed using SPSS 16. The PMR medians were 3.25 (95% CI: 0.1–100) and 0.1 (95% CI: 0.07–1) in the stool samples of CRC patients and healthy individuals, respectively. The results showed a significant difference in <i>CDX1</i> gene PMR between stool samples of CRC patients and controls (<i>P</i>-value &lt;0.001). According to the results of this study, it can be argued that measurement of <i>CDX1</i> gene DNA in stool samples using the MethyLight PCR has acceptable sensitivity and specificity, and is adequately potential to be used as a noninvasive complementary method for the diagnosis of CRC, along with colonoscopy as the gold standard to this end. This study is the first report on <i>CDX1</i> methylation in stool samples of CRC patients. Therefore, further research should be carried out with a larger sample size to evaluate its efficacy as a diagnostic biomarker in clinical laboratories.</p>","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"31 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141511349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}