Meta Gene最新文献

{"title":"Study of the potential association of the BCHE rs1803274 genetic polymorphism and serum level of its protein with breast cancer","authors":"Mona S. Habieb ,&nbsp;Nesreen G. Elhelbawy ,&nbsp;Alshimaa M. Alhanafy ,&nbsp;Mohammad G. Elhelbawy ,&nbsp;Ahmed S. Alkelany ,&nbsp;Amany M. Wahb","doi":"10.1016/j.mgene.2021.100913","DOIUrl":"10.1016/j.mgene.2021.100913","url":null,"abstract":"<div><h3>Background</h3><p>Genetic-based individual differences remain a promising area for studying cancer susceptibility. BCHE gene encodes the butyrylcholinesterase (BChE) enzyme, which has been linked to inflammation and tumor genesis. The commonest missense mutation of BCHE gene is the rs1803274 G/A polymorphism. We aimed to analyze BCHE rs1803274 gene polymorphism in terms of distribution among breast cancer patients, its effect on enzyme activity and its correlation with clinic pathological parameters.</p></div><div><h3>Methods</h3><p>160 breast cancer female patients matched by age with 120 female healthy controls were recruited. CA 15–3 and CEA were measured by ELISA. BChE activity was measured by spectrophotometry. BCHE rs1803274 polymorphism was analyzed by real time- PCR.</p></div><div><h3>Results</h3><p>Significant higher prevalence of GA genotype and A allele were observed in patients [<em>P</em> &lt; 0.001, OR (95% CI); 3.12 (1.67–5.85), <em>P</em> &lt; 0.001, OR (95% CI); 2.86 (1.68–4.87) respectively]. This significance was observed under the dominant mode of inheritance (<em>P</em> &lt; 0.001, OR (95% CI); 3.22 (1.78–5.85). GA + AA patients showed significant association with tumor grade, stage, and metastasis (P &lt; 0.001). GA + AA patients exhibited significantly lower BChE activity compared to GG patients (3648.5 (2968–4332) mU/ml and 7128.5 (6332–8341) mU/ml respectively, <em>P</em> &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>Higher frequency of the A-variant of BCHE rs1803274 and the associated low activity of BChE in breast cancer patients could represent susceptibility elements for development of breast cancer. Moreover, the rs1803274 is linked to some tumor features, which could be a proof of its prognostic value.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100913"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43286764","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":"Atypical phenotype in a patient with ceruloplasmin mutations in the compound heterozygous state","authors":"Giulia Ravasi ,&nbsp;Sara Pelucchi ,&nbsp;Francesco Canonico ,&nbsp;Raffaella Mariani ,&nbsp;Alberto Piperno","doi":"10.1016/j.mgene.2021.100905","DOIUrl":"10.1016/j.mgene.2021.100905","url":null,"abstract":"<div><p>Aceruloplasminemia is an ultra-rare and fatal autosomal recessive disease with a long lasting neurological disabling period of life caused by mutations in ceruloplasmin gene. Disease phenotype is heterogeneous and variably characterized by iron-restricted erythropoiesis and microcytic anemia, hyperferritinemia with tissue iron accumulation in liver, pancreas and brain, diabetes, retinopathy and neurodegeneration. Although most heterozygotes are asymptomatic, they might present with significant neurological symptoms at some point in their lives. We report here a patient with hyperferritinemia and severe depressive disorder, harbouring two mutations in ceruloplasmin in the compound heterozygous state (p.Pro477Leu and p.Gly895Ala). Both mutations are classified as deleterious <em>in silico</em>, but <em>in vitro</em> functional study partially confirmed it. Our findings suggest that the two mutations cooperate in inducing low ceruloplasmin production in the range observed in aceruloplasminemia heterozygotes and raise the question whether this might increase patient's susceptibility to neurologic manifestations.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100905"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41811241","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":"Polymorphisms in GLIS3 and susceptibility to diabetes mellitus: A systematic review and meta-analysis","authors":"Guilherme Coutinho Kullmann Duarte ,&nbsp;Tais Silveira Assmann ,&nbsp;Bianca Marmontel de Souza ,&nbsp;Daisy Crispim","doi":"10.1016/j.mgene.2021.100898","DOIUrl":"10.1016/j.mgene.2021.100898","url":null,"abstract":"<div><p>The transcription factor Gli-similar 3 (GLIS3) has an important role in the development, survival and proliferation of pancreatic beta-cells and insulin gene expression regulation. Accordingly, genome-wide association studies have shown <em>GLIS3</em> gene confers risk to both type 1 and type 2 diabetes mellitus (DM). However, data on the association of individual <em>GLIS3</em> polymorphisms with DM are still inconclusive. Thus, this systematic review and meta-analysis was aimed to scrutinize the potential association between <em>GLIS3</em> polymorphisms and DM. A literature search was carried out in EMBASE and PubMed resources to find all studies that analyzed <em>GLIS3</em> polymorphisms regarding susceptibility to DM. Following the eligibility criteria, 25 studies were included in this systematic review. Twelve of them had complete data available, allowing meta-analyses (T1DM: 3 studies with rs7020673 polymorphism and 3 with rs10758593; T2DM: 6 with rs7034200 polymorphism and 3 with rs7041847). The rs7020673 and rs10758593 polymorphisms were not associated with T1DM. Regarding T2DM studies, the rs7041847A and the rs7034200C alleles were associated with risk for T2DM (OR = 1.08, 95% CI 1.00–1.16 and OR = 1.17, 95% CI 1.09–1.26; considering the allele contrast model). In conclusion, <em>GLIS3</em> rs7034200 and rs7041847 polymorphisms seem to confer risk for T2DM. Additional studies are needed to confirm whether <em>GLIS3</em> polymorphisms are associated with DM.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100898"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100898","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46986306","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":"Interleukin-33 gene variants (rs928413, rs16924159 and rs7037276) and susceptibility to asthma among Iraqi adult patients","authors":"Semaa A. Shaban ,&nbsp;Suad A. Brakhas ,&nbsp;Ali H. Ad'hiah","doi":"10.1016/j.mgene.2021.100907","DOIUrl":"10.1016/j.mgene.2021.100907","url":null,"abstract":"<div><p>Interleukin-33 is proposed to influence asthma susceptibility. Three <em>IL33</em> gene variants (rs928413, rs16924159 and rs7037276) were included in a case-control study conducted on 104 Iraqi asthmatics and 111 controls. Tetra-primer-amplification-refractory-mutation-system-polymerase-chain-reaction method was used to determine these variants. Logistic regression analysis showed that <em>A</em> allele and AA genotype of rs928413 were significantly associated with an increased asthma risk under allele and recessive models, respectively. Regarding rs16924159, allele, recessive, dominant and codominant models demonstrated a significant association with asthma susceptibility, but the highest risk was found for AA genotype under recessive model. For SNP rs7037276, neither alleles nor genotypes were associated with asthma risk. Tri-locus haplotype analysis (in the order rs928413, rs16924159 and rs7037276) revealed that A-G-T haplotype frequency was significantly elevated in asthmatics compared to controls, while frequency of G-G-T haplotype was significantly decreased. In conclusions, two <em>IL33</em> gene SNPs (rs928413 and rs16924159) were proposed to be associated with asthma susceptibility.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100907"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43568170","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 and cytogenetic screening of autistic spectrum disorder: Genotype-phenotype profiles","authors":"Arun Meyyazhagan ,&nbsp;Balamuralikrishnan Balasubramanian ,&nbsp;Haripriya Kuchi Bhotla ,&nbsp;Murugesh Easwaran ,&nbsp;Sureshkumar Shanmugam ,&nbsp;Karthick Kumar Alagamuthu ,&nbsp;Vijaya Anand Arumugam ,&nbsp;Sasikala Keshavarao ,&nbsp;Manikantan Pappusamy","doi":"10.1016/j.mgene.2021.100924","DOIUrl":"10.1016/j.mgene.2021.100924","url":null,"abstract":"<div><p>Autism, a pervasive developmental disorder typically characterized by repetitive behaviour, social skills deficit (or a deficit in social communication), speech and language impairments. Our prime focus is to analyze the clinical features and phenotypical behavioural changes using the diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM IV-TR), and locating the biomarkers associated with specific autistic characters using karyotyping and fluorescence <em>in situ</em> hybridization (FISH) techniques. The prevalence rate of the <em>neurexin</em> 1 <em>(NRXN1)</em> gene polymorphism was also assessed in the current study. The study group involved 196 samples with 98 autistics, and equal age-matched (±2) controls based on their birth order and carrier. The participants include 35.2% males (<em>n</em> = 69) and 14.8% females (<em>n</em> = 29). The autistic and control participants were categorized based on their ages as group I (&lt;12 yrs) with <em>n</em> = 62; males <em>n</em> <em>=</em> 41 (20.9%); females <em>n</em> <em>=</em> 21 (10.7%) and group II (≥12 yrs)-<em>n</em> = 36; males <em>n</em> <em>=</em> 28 (14.2%); females <em>n</em> <em>=</em> 08 (4.08%). Karyotyping was done for autism participants (<em>n</em> = 98) and the results showed that 90% of autistic participants were either the only child or the first child with a low perception and frequency in both the groups. Subsequently, we carried out the FISH assay on participants <u>(</u><em>n</em> = 37) with higher DSM-IV TR score (≥30<u>)</u>. Only 30 FISH tests were negative for subtelomeric deletions with <em>NRXN1</em> polymorphism genotypic frequency as 62.50%, 25% and 25% for A/A, A/G and G/G genotype respectively. Our study suggests the link between a haplotype with clinical signs of autism for the single nucleotide sequence (SNP rs9636391) and links autistic characters and gene among autistic children according to their birth order, age and gender in India.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100924"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42406859","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":"Associations of INPPL1 (+1893CC/AA and + 2945AA/GG) exonic polymorphisms with the risk of type 2 diabetes mellitus in North Indian population: A case control study","authors":"Jaswinder Singh ,&nbsp;Vikas Kumar ,&nbsp;Kiran Bala ,&nbsp;Ashish Aneja ,&nbsp;Jasbir Singh","doi":"10.1016/j.mgene.2021.100929","DOIUrl":"10.1016/j.mgene.2021.100929","url":null,"abstract":"<div><h3>Background and aim</h3><p><em>INPPL1</em> gene encodes a lipid phosphatase Src homology 2-containing 5′-inositol phosphatase 2 (SHIP2) which is involved in the negative regulation of insulin signaling. In the light of several association studies of <em>INPPL1</em> gene polymorphisms with T2DM, and the absence of association studies from India, present study was conducted to assess the association of two SNPs of <em>INPPL1</em> gene with T2DM risk in North Indian population.</p></div><div><h3>Material and method</h3><p>Two single nucleotide polymorphism (SNPs) (+1893CC/AA and + 2945AA/GG) in <em>INPPL1</em> gene were genotyped in total of 270 subjects with PCR-RFLP genotyping method.</p></div><div><h3>Results</h3><p>It was observed that, out of the two SNPs, only +1893CC/AA was found to be significantly associated with T2DM and frequency of A allele (C vs A, <em>p</em> = 0.002) has been found to be significantly higher in T2DM cases. Strong linkage disequilibrium was observed between two SNPs as assessed through D′ and r² (D′ = 0.984, r² = 0.009) and AG haplotype (OR = 3.59, 95% CI (1.59–9.80), <em>p</em> = 0.0015) was associated with increased risk of T2DM while CG haplotype (OR = 0.54, 95% CI (0.33–0.88) <em>p</em> = 0.012) significantly decreases the risk of developing T2DM. Regression analysis showed that SNP +1893CC/AA is associated with T2DM risk when adjusted for clinical/demographic variables.</p></div><div><h3>Conclusion</h3><p>Results showed that <em>INPPL1</em> gene polymorphism +1893CC/AA may increase susceptibility to T2DM and ‘A' allele might be serving as a risk factor in development of T2DM in Indian population.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100929"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100929","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46135693","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":"Human leukocyte antigens (HLA) association with myasthenia gravis (MG) and its myasthenia manifestations in Algerian patients","authors":"Bouchtout Mohamed Nadji ,&nbsp;Meçabih Fethi ,&nbsp;Mihoubi Esma ,&nbsp;Boukadir Chahrazad ,&nbsp;Attal Elias ,&nbsp;Daoudi Smail ,&nbsp;Touil-Boukoffa Chafia ,&nbsp;Raache Rachida ,&nbsp;Attal Nabila","doi":"10.1016/j.mgene.2021.100937","DOIUrl":"10.1016/j.mgene.2021.100937","url":null,"abstract":"<div><h3>Background</h3><p>Myasthenia gravis (MG) is an autoimmune disease with a well-established involvement of genetic factors.</p></div><div><h3>Aim</h3><p>this study was to assess the human leukocyte antigens (HLA) genes association with myasthenia gravis and its myasthenic manifestations.</p></div><div><h3>Methods</h3><p>We performed a case-control study where twenty eight patients and one hundred and nine healthy subjects were included. A subgroup of generalized and acetylcholine receptor antibodies positive myasthenia gravis was examined for myasthenic manifestations associations. HLA genotyping was performed by polymerase chain reaction- sequence specific oligonucleotide (PCR-SSO) method.</p></div><div><h3>Results</h3><p>On one hand, HLA A*30 and DRB1*04 alleles were more frequent among patients with myasthenia gravis whereas A*02 and B*49 were less frequent (<em>p</em> &lt; 0.05). On the other hand, B*08 was positively associated with limb muscles weakness and negatively association with dysphagia while B*44 and DRB1*03 were both positively associate with cervical muscles weakness (<em>p</em> &lt; 0.05).</p></div><div><h3>Conclusion</h3><p>Our results suggest the association of various HLA alleles with myasthenia gravis and some of its myasthenic manifestations. However, further studies are required support these findings and clarify the underlying mechanisms.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100937"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100937","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46291964","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":"Association of methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes promoter methylation pattern with the risk of essential hypertension","authors":"Shabnaz Koochakkhani ,&nbsp;Fatemeh Nabizadeh ,&nbsp;Azim Nejatizadeh ,&nbsp;Ebrahim Eftekhar","doi":"10.1016/j.mgene.2021.100914","DOIUrl":"10.1016/j.mgene.2021.100914","url":null,"abstract":"<div><p>Methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) are key enzymes in the metabolism of homocysteine pathway whose dysfunction can lead to essential hypertension (EH). This study aimed to investigate the possible association of <em>MTHFR</em> and <em>CBS</em> genes promoter methylation patterns with the risk of EH. We also aimed to search differentially expressed microRNAs (miRs) and demonstrate the role of miRs in the aberrant DNA methylation in essential hypertensive patients by targeting DNA methyltransferases (DNMTs).</p><p>20 essential hypertensive patients and 20 healthy controls were selected. DNA methylation levels of 10 CpG dinucleotides on <em>MTHFR</em> and 19 CpG dinucleotides on <em>CBS</em> genes promoter was measured using Bisulfite-Sequencing PCR (BSP). The GSE118578 profile was downloaded from the GEO database to identify differentially expressed miRs in hypertensive patients and R statistical software was used to analyze the data. Enrichment analysis was conducted to predict target genes using databases of Targetscan, and miRDB-MicroRNA Target Prediction Database.</p><p>No significant association between <em>MTHFR</em> gene methylation and EH was observed. There was a significant association between one of the CpG sites of <em>CBS</em> gene promoter (CpG19 (+1035C)) and EH [OR = 5.3(0.895–31.393), <em>p</em> = 0.047]. Furthermore, we reported a list of miRs that may have an essential role in regulating DNA methylation by targeting DNMTs.</p><p>Our findings showed that hypermethylation of CpG19 (+1035C) of <em>CBS</em> gene promoter could increase the risk of EH. Methylation status of <em>MTHFR</em> gene had no significant association with EH. Also, in-silico investigation showed that miRs may affect aberrant genes methylation through altering DNMTs biogenesis.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100914"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100914","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47462146","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 association of DISC1 variant rs3738401 with susceptibility to Schizophrenia risk in North Indian population","authors":"Indu Priya ,&nbsp;Isar Sharma ,&nbsp;Sakshi Sharma ,&nbsp;Suruchi Gupta ,&nbsp;Manu Arora ,&nbsp;G.H. Rasool Bhat ,&nbsp;Ritu Mahajan ,&nbsp;Nisha Kapoor","doi":"10.1016/j.mgene.2021.100923","DOIUrl":"10.1016/j.mgene.2021.100923","url":null,"abstract":"<div><p>DISC1 regulates signalling pathways which are involved in neuronal development, brain maturation like neuronal proliferation and processes involved in central nervous system development. The DISC1 gene is one of the potential candidate gene involved in Schizophrenia risk. In the present study, we performed case-control association study using TaqMan based chemistry in which a total of 382 individuals, 152 Schizophrenia patients and 230 healthy controls were genotyped to explore the association of rs3738401 and rs16854954 of DISC1 gene with susceptibility to Schizophrenia risk in North Indian population of Jammu region. The findings from the study revealed that rs3738401 was significantly associated with Schizophrenia and the G allele of rs3738401 is associated with increased risk for the disorder (OR = 1.66; [1.22–2.24 at 95%CI] P = 0.001) whereas other variant rs16854954 of DISC1 gene was not found to be associated with the disease(OR = 0.96, [0.71–1.30 at 95% CI] P = 0.75). The present study offers an important evidence on the genetic cause of DISC1 gene in North Indian population and further strengthens the GWAS findings on the role of DISC1 in schizophrenia risk. This study provides the holistic view about the Schizophrenia in Jammu region, North Indian population and it can be a hallmark if verified on a very large sample size (cohort).</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100923"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100923","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48181037","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":"Novel association of PhosphoSerine PHosphatase (PSPH) gene mutations with male infertility identified through whole exome sequencing of South Indians","authors":"Golnaz Shemshaki ,&nbsp;Mohsen Najafi ,&nbsp;Ashitha S. Niranjana Murthy ,&nbsp;Suttur S. Malini","doi":"10.1016/j.mgene.2021.100897","DOIUrl":"10.1016/j.mgene.2021.100897","url":null,"abstract":"<div><p>Male infertility (MI) is mainly caused by spermatogenic failure, and despite long years of assisted reproductive therapy, a significant number of cases remain idiopathic. Oligoasthenozoospermia (OA) is one of the most severe idiopathic MI forms, conditioned with decreased sperm motility and count. However, its pathology remains unclear, but few genetic factors have been identified. The main aim of this study was to find genetic variations in spermatogenic genes with severe OA. Semen and blood samples were collected from 250 MI subjects. Semen analysis, karyotyping, and Y microdeletion was performed to retain purely idiopathic MI cases (<em>n</em> = 247). 40 OA cases were identified, of which four severe cases were subjected to whole-exome sequencing, bioinformatics analyses, and pathway analysis, followed by validation of pathogenic variants in the remaining 36 OA cases through Sanger sequencing. We identified six variants in exon5 of gene <em>PSPH,</em> of which four variants were predicted to be pathogenic and two damaging mutations in exon4. In this study, we propose the novel role of <em>the PSPH</em> gene in their different mechanistic pathways. Detailed pathway analysis of enzyme PSPH involved in <span>l</span>-serine biosynthesis demonstrated that its dysfunction could cause a decrease in sperm count and sperm motility. The hypothesized function of PSPH in eliciting OA has been described.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100897"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54836193","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}