Genetic testing and molecular biomarkers最新文献

{"title":"Biomarker-Guided Diagnosis of Riboflavin Transporter Deficiency Presenting as Seronegative Myasthenia Gravis: A Short Report from a Consanguineous Family.","authors":"Muhammad Wasim, Iram Javed, Guoda Ma","doi":"10.1177/19450265261493084","DOIUrl":"10.1177/19450265261493084","url":null,"abstract":"<p><strong>Background: </strong>Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare, treatable neurodegenerative disorder caused by riboflavin transporter gene variants (SLC52A2, SLC52A3). Early symptoms can mimic neuromuscular junction disorders, causing diagnostic delays.</p><p><strong>Case presentation: </strong>A 3.5-year-old girl from consanguineous parents presented at 2.5 years with isolated bilateral ptosis, later developing dysphagia, dysphonia, facial diplegia, stridor, and respiratory compromise. Examination revealed tongue atrophy with fasciculations and bulbar weakness but normal limb strength. Diagnosed with seronegative myasthenia gravis, she failed to respond to corticosteroids, pyridostigmine, salbutamol, and intravenous immunoglobulin. Absence of fatigability, lower motor neuron signs, and a sibling history of hearing loss and bulbar palsy prompted genetic testing revealed a homozygous missense variant in <i>SLC52A3</i> (c.670T > C; p.Phe224Leu). High-dose riboflavin (up to 50 mg/kg/day) led to gradual improvement in bulbar function, resolution of stridor, and respiratory stabilization, though ptosis and tongue fasciculations persisted.</p><p><strong>Conclusion: </strong>This report is novel in using clinical response to riboflavin as a functional biomarker for riboflavin transporter deficiency (RTD) in a patient with a variant of uncertain significance, unlike prior cases with definitive genetics. Empiric riboflavin challenge offers a practical framework when genetic results are ambiguous. RTD should be suspected in children with treatment-resistant, non-fluctuating ptosis and bulbar weakness, particularly with consanguinity or family history of hearing loss and bulbar palsy. Early high-dose riboflavin prevents decline, while immunosuppression is ineffective and potentially harmful.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"283-288"},"PeriodicalIF":1.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060203","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":"Fat Mass and Obesity Associated (FTO) and Melanocortin 4 Receptor (MC4R) Gene Variants as Prognostic Markers of Obesity in Quetta City.","authors":"Nadia Ewaz Ali, Nabeela Tariq","doi":"10.1177/19450265261481765","DOIUrl":"10.1177/19450265261481765","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a complex condition caused by environmental and hereditary factors. Single nucleotide polymorphisms (SNPs) in the FTO (rs9939609) and melanocortin-4-receptor (MC4R) (rs17782313) genes have been strongly linked to an increased risk of obesity. This study sought to determine the relationship between these polymorphisms and their combined effects on the risk of obesity in Quetta, Pakistan.</p><p><strong>Methods: </strong>A total of 250 individuals (150 obese and 100 non-obese) aged 18-65 were recruited from Sardar Bahadur Khan Women's University, Bolan Medical Complex Hospital, and the overall Quetta population. Anthropometric measurements, lifestyle characteristics, and demographic information were gathered using standardized questionnaires. The fat mass and obesity associated FTO rs9939609 and Melanocortin-4-receptor MC4R rs17782313 genes were genotyped using the amplification refractory mutation system polymerase chain reaction method.</p><p><strong>Results: </strong>Both SNPs were associated with obesity across multiple genetic models. For FTO rs9939609, the risk variant significantly increased obesity susceptibility under co-dominant (odds ratio [OR] = 4.13, <i>p</i> = 0.010), recessive (OR = 3.44, <i>p</i> = 0.011), and dominant (OR = 1.91, <i>p</i> = 0.013) models; Similarly, the MC4R rs17782313 variant demonstrated robust association in co-dominant (OR = 3.33 and 3.64, <i>p</i> = 0.009), recessive (OR = 3.37, <i>p</i> = 0.002), and dominant models (OR = 1.88, <i>p</i> = 0.037). Both SNPs deviated from Hardy-Weinberg equilibrium in the obese group, indicating possible selection pressure; risk genotypes were also significantly associated with higher body mass index, weight, and waist-hip ratio (<i>p</i> < 0.05). Furthermore, combined genotype analysis revealed that the MC4R/FTO variant combination TT/AA (OR = 0.19, <i>p</i> = 0.006) and CC/AT (OR = 0.12, <i>p</i> = 0.002) were significantly predictive of obesity status compared to the wild-type baseline.</p><p><strong>Conclusion: </strong>This study shows a clear correlation between the higher incidence of obesity in Quetta, Pakistan, and the FTO rs9939609 and MC4R rs17782313 polymorphisms. These results of the study play an important role in genetic screening for the evaluation of obesity risk and play an essential role in research related to the role of genetic variables in public health initiatives aimed at preventing obesity.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"289-297"},"PeriodicalIF":1.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905909","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":"TGFBI p.H626R Mutation in a Chinese Family with Lattice Corneal Dystrophy: A Short Report and Literature Review.","authors":"Xuan Lu, Ke Zhang, Rubing Liu, Zebin Li, Beiling Tan, Han Wang, Shuyi Chen, Mingbing Zeng","doi":"10.1177/19450265261477354","DOIUrl":"10.1177/19450265261477354","url":null,"abstract":"<p><strong>Purpose: </strong>To report a Chinese family with lattice corneal dystrophy (LCD) caused by the TGFBI p.H626R mutation and summarize its clinical and genetic characteristics through a literature review.</p><p><strong>Methods: </strong>A three-generation Chinese family with LCD was investigated through detailed ophthalmic examination. Whole-exome sequencing followed by Sanger sequencing was performed to identify candidate variants. Bioinformatics tools were used to evaluate pathogenicity. Previously reported cases of H626R-associated LCD were reviewed.</p><p><strong>Results: </strong>A heterozygous TGFBI mutation (c.1877A>G; p.His626Arg) was identified in affected individuals. All patients underwent penetrating keratoplasty at advanced stages, with improved postoperative visual acuity. A pooled analysis of 109 patients from at least 12 countries indicated that H626R-associated LCD is characterized by recurrent corneal erosions, asymmetrical progression, and thick lattice lines extending toward the corneal periphery.</p><p><strong>Conclusions: </strong>The TGFBI p.H626R mutation is associated with a distinct LCD phenotype and contributes to disease progression. Most affected individuals underwent penetrating keratoplasty at the advanced stage of the disease to restore visual acuity.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"278-282"},"PeriodicalIF":1.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712032","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":"The Impacts of <i>MTHFR</i> C677T Variant (rs1801133) on Cardiometabolic Profiles and Early Onset Coronary Artery Disease: A Case-Control Study.","authors":"Guiqing Wang, Shengping Wang, Hang Li, Baozhu Wei, Zhi Luo","doi":"10.1177/19450265261491102","DOIUrl":"10.1177/19450265261491102","url":null,"abstract":"<p><strong>Background: </strong>The <i>MTHFR</i> C677T polymorphism (rs1801133) is a well-documented genetic variant in cardiovascular research, yet its mechanistic role in early onset coronary artery disease (EOCAD) remains poorly characterized in East Asian populations. This study aimed to explore whether rs1801133 modulates EOCAD risk by altering proatherogenic cardiometabolic traits in the Chinese Han population.</p><p><strong>Methods: </strong>This rigorous case-control study enrolled 128 patients with angiographically confirmed EOCAD and 100 age- and sex-matched controls with nonobstructive coronary arteries. Standard enzymatic assays were used to detect blood lipid profiles and one-carbon metabolic markers. We constructed prediction models integrating conventional cardiometabolic risk factors with rs1801133. Model incremental performance was evaluated via integrated discrimination improvement (IDI) and net reclassification improvement (NRI), with 1000 bootstrap replicates for internal validation.</p><p><strong>Results: </strong>The rs1801133 T allele was significantly associated with higher EOCAD susceptibility. Compared with CC carriers, TT genotype individuals exhibited adverse cardiometabolic profiles, including elevated low-density lipoprotein cholesterol (LDL-C) (3.22 ± 0.48 vs. 2.83 ± 0.85 mmol/L, <i>p</i> < 0.05), systolic blood pressure (145.25 ± 25.28 vs. 133.03 ± 19.89 mmHg, <i>p</i> = 0.01), diastolic blood pressure (90.31 ± 15.56 vs. 85.68 ± 13.19 mmHg, <i>p</i> = 0.04), and homocysteine (16.98 ± 9.48 vs. 12.67 ± 4.47 μmol/L, <i>p</i> < 0.05). Receiver operating characteristic (ROC) analysis identified LDL-C as the dominant EOCAD predictor, and logistic regression confirmed rs1801133 as an independent risk factor. Adding rs1801133 to the base model significantly improved IDI (0.022, <i>p</i> = 0.012) and NRI (0.291, <i>p</i> = 0.040). Bootstrap validation with minimal model optimism (0.034-0.036) verified favorable internal stability.</p><p><strong>Conclusions: </strong>rs1801133 is a functional genetic determinant of EOCAD in the Chinese Han population. The TT genotype defines a high-risk subgroup aggravated by combined dyslipidemia and hyperhomocysteinemia. rs1801133 yielded significant incremental discrimination and reclassification value over traditional risk factors. These findings support personalized EOCAD risk stratification, highlighting intensive LDL-C management for T allele carriers as a promising early intervention strategy.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"298-306"},"PeriodicalIF":1.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060221","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":"Clinical Evaluation of miR-135b-5p and miR-21-5p Expression on Self-Collected Cervical Swab Samples for Triaging HR-HPV-Positive High-Grade Preneoplastic Lesions in India.","authors":"Farhin Sultana, Ananya De, Sreeya Bose, Anirban Roychowdhury, Masmuda Khatun, Puja Chatterjee, Manisha Vernekar, Dipanwita Banerjee, Jayanta Chakrabarti, Ranajit Kumar Mandal, Chinmay Kumar Panda, Sankhadeep Dutta","doi":"10.1177/19450265261491098","DOIUrl":"10.1177/19450265261491098","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the triage performance of microRNA (miRNA) biomarkers on self-collected, high-risk human papillomavirus (HR-HPV)-positive cervical swabs to discern cervical intraepithelial neoplasia II-III or high-grade squamous intraepithelial lesions (HSIL) in Indian women for precise diagnosis and treatment prioritization.</p><p><strong>Methods: </strong>Through <i>in silico</i> analysis, miR-135b-5p and miR-21-5p were identified as upregulated and amplified miRNAs in cervical cancer (CaCx). Quantitative real-time PCR was used to assess miR-135b-5p and miR-21-5p and their targeting, LIM domain-containing protein 1 (LIMD1) and von Hippel-Lindau (VHL) messenger RNA (mRNA) expression, in a discovery cohort (<i>N</i> = 42; normal cervical epithelium [<i>N</i> = 9], CIN [<i>N</i> = 12], and CaCx [<i>N</i> = 21] tissue samples). Thereafter, miRNA expression was validated in an independent set of self-collected cervical swabs (<i>N</i> = 243; HR-HPV-positive [asymptomatic (<i>N</i> = 52), low-grade squamous intraepithelial lesions (LSIL) (<i>N</i> = 50), and HSIL (<i>N</i> = 52), CaCx (<i>N</i> = 35)] and HPV-negative normal [<i>N</i> = 54]). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of these two candidate miRNAs.</p><p><strong>Results: </strong>In discovery-phase samples, miR-135b-5p showed progressive upregulation from CIN (<i>p</i> = 0.056) to CaCx (<i>p</i> = 0.012), while miR-21-5p showed significant overexpression at CIN (<i>p</i> = 0.011) and CaCx (<i>p</i> = 0.005) compared to normal tissue. Concurrently, significant downregulation of LIMD1/VHL mRNA expression was observed in the same CaCx samples. In the validation cohort, miR-135b-5p and miR-21-5p were significantly overexpressed in HSIL samples compared to lower-grade lesions (≤LSIL), with a corresponding downexpression of LIMD1/VHL. ROC curve analysis demonstrated high sensitivity and specificity for miR-21-5p and miR-135b-5p-both individually and in combination-for distinguishing HR-HPV + HSIL from LSIL, asymptomatic, or HPV-negative normal samples.</p><p><strong>Conclusion: </strong>miR-135b-5p and miR-21-5p constitute a feasible triage biomarker on noninvasive, self-collected cervical swab samples for early, precise diagnosis of women with HR-HPV-positive HSIL, requiring treatment prioritization in low-resource settings.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"264-275"},"PeriodicalIF":1.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037972","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":"Association of Interleukin-27 Gene Variants with Susceptibility to Brucellosis Among Iranian Population: A Case-Control Study.","authors":"Mehdi Kalani, Erfane Fattah, Sadaf Asaei, Maral Choopanizadeh, Mahtab Kalani, Leila Saffar, Hojat Shahbazi, Ali Moravej, Zahra Montaseri","doi":"10.1177/19450265261491082","DOIUrl":"10.1177/19450265261491082","url":null,"abstract":"<p><strong>Objectives: </strong>Brucellosis is recognized as one of the most widespread zoonotic diseases, caused by facultative intracellular coccobacilli of the genus <i>Brucella</i>. Interleukin-27 (IL-27) is a pleiotropic cytokine that serves a critical role in the development of immunity against <i>Brucella</i>. IL-27 single nucleotide polymorphisms (SNPs) may influence susceptibility to brucellosis by altering the expression and/or function of this cytokine. This study sought to examine the potential association between IL-27 genetic polymorphisms and brucellosis susceptibility among Iranian individuals.</p><p><strong>Methods: </strong>The study comprised 207 patients diagnosed with brucellosis and 82 healthy livestock workers as controls matched geographically to the patients' population. IL-27 SNPs at positions -964 A/G, 2905 T/G, and 4730 T/C were genotyped and then evaluated through case-control comparisons.</p><p><strong>Results: </strong>Genotype analysis revealed a significantly higher frequency of the TG genotype at rs17855750 in controls compared to patients (<i>p</i> = 0.0002). Conversely, the TT genotype at rs17855750 and the CC genotype at rs181206 were more frequent in patients (<i>p</i> = 0.012 and <i>p</i> = 0.026, respectively). Furthermore, specific haplotypes (AGT and GGT) and haplogenotypes (ATT/AGT, GTC/GGT, and ATT/GTT) showed a significantly different distribution between the groups, being more prevalent in controls.</p><p><strong>Conclusion: </strong>This study provides evidence for an association between IL-27 gene variants and brucellosis susceptibility, reinforcing the role of host genetics in <i>Brucella</i> infection. These findings not only enhance our understanding of brucellosis pathogenesis but also pave the way for genetic-based risk assessment and the development of novel therapeutic strategies.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"255-263"},"PeriodicalIF":1.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037950","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":"Integrative Genetic and Bioinformatic Analysis of Androgen Pathway Gene Polymorphisms, Testosterone, and PSA Levels in Prostate Cancer.","authors":"Ghasem Ghorbani Vale Zaghard, Mehdi Haghi, Mehdi Ghiamirad, Saeid Ghorbian, Mehdi Ebrahimi","doi":"10.1177/19450265261488655","DOIUrl":"10.1177/19450265261488655","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is genetically a complicated disease with mediation by variations in genes coding for androgen biosynthesis and signaling genes. In the current study, we investigate the associations of key polymorphisms in the androgen pathway with serum testosterone and prostate-specific antigen (PSA) levels, while also exploring their potential functional impact using bioinformatics analyses.</p><p><strong>Methods: </strong>A total of 314 patients with prostate adenocarcinoma and 287 age-matched healthy controls were genotyped for ten SNPs across CYP17A1, HSD3B1, HSD3B2, SRD5A2, and AR genes using sequencing methods. Associations with disease risk, serum testosterone, and PSA were evaluated. Functional predictions, linkage disequilibrium (LD), and protein-protein interaction (PPI) network analyses were performed <i>in silico</i>.</p><p><strong>Results: </strong>Significant associations were found for CYP17A1 (rs10883783), HSD3B1 (rs6203, rs33937873), SRD5A2 (rs12470143) with PCa risk, whereas androgen receptors polymorphisms (rs1204038, rs6152) and HSD3B2 (rs1819698, rs58154933) showed no association. The A allele of CYP17A1 rs10883783 and the T allele of HSD3B1 rs6203 were correlated with lower testosterone levels, while only the CYP17A1 rs10883783 polymorphism was significantly associated with increased PSA levels. Bioinformatic analysis showed potential deleterious effects for the HSD3B1 rs6203 variant, as well as regulatory effects for CYP17A1 rs10883783, in accordance with their corresponding enzymatic role in androgen biosynthesis. Additionally, analysis of PPI and co-expression networks revealed tight functional connectivity of the androgen pathway genes.</p><p><strong>Conclusion: </strong>These results suggest a biological function for genetic polymorphisms of HSD3B1 and CYP17A1 in PCa susceptibility and androgen regulation. These polymorphic variants can serve as effective risk biomarkers for PCa and disease activity using a combination of genotyping, hormone assay, and bioinformatics. These findings need more research, including larger multi-ethnic cohorts and functional validation to ascertain their therapeutic relevance.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"242-254"},"PeriodicalIF":1.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012202","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":"The Expression Profile of microRNA Genes and NT-proBNP as Possible Predictors of One-Year Mortality in Egyptian Adults with Acute Heart Failure: A Prospective Biomarker Study.","authors":"Haidy Magdy, Radwa M Abdel Halim, May M Selim, Emmanuel Fares, Mona Abou El Hassan, Nehad Mosaad","doi":"10.1177/19450265261470709","DOIUrl":"10.1177/19450265261470709","url":null,"abstract":"<p><strong>Background: </strong>Acute heart failure (AHF) is a prevalent and life-threatening condition that is associated with high morbidity and mortality, particularly in adults. MicroRNAs (miRNAs) have been identified as potential biomarkers in various cardiovascular diseases. Specifically, miR-302b-3p and miR-103 have demonstrated potential as biomarkers in heart failure.</p><p><strong>Objectives: </strong>This study aims to investigate the diagnostic and prognostic potential of circulating miR-302b-3p and miR-103 in AHF among Egyptian adults and the association between these miRNAs and NT-proBNP levels.</p><p><strong>Methods: </strong>The study involved 95 participants, comprising 45 Egyptian adults diagnosed with AHF and 50 age- and gender-matched healthy controls. Circulating levels of miR-302b-3p and miR-103 were measured using qRT-PCR, while NT-ProBNP levels were determined via enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>The expression of miR-302b-3p was significantly decreased in patients with AHF compared with healthy controls (<i>p</i> < 0.05). The levels of this miRNA showed a significant negative correlation with NT-proBNP levels (<i>r</i> = 0.78, <i>p</i> = 0.013). Lower levels of miR-302b-3p and increased NT-ProBNP levels correlated with more severe prognosis, including higher rates of hospitalization and 1-year mortality in patients with AHF (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>NT-ProBNP and miR-302b-3p serve as a promising biomarker for the diagnosis and prognosis of AHF in Egyptian adults that can further guide health care professionals for risk stratification and therapeutic response.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"233-240"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148601806","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 Short Indel is Causing Biotinidase Deficiency in a 4-Month-Old Boy from Jammu and Kashmir.","authors":"Rama Sharma, Anuj Bhatti, Darshpreet Singh, Nisha Kapoor, Subramaniya Bharathiraja, Sanjana Kaul, Ankit Mahajan, Manoj Kumar Dhar","doi":"10.1177/19450265261469732","DOIUrl":"10.1177/19450265261469732","url":null,"abstract":"<p><strong>Background: </strong>Biotinidase is an enzyme recycling endogenous biotin by hydrolyzing ε-<i>N</i>-biotinyl lysine (biocytin) to lysine and biotin. Biotin acts as a coenzyme in various carboxylation reactions. Biotinidase deficiency is rare, with an incidence of 1 per 112,271 individuals.</p><p><strong>Objectives: </strong>Genetic characterization of a 4-month-old boy born out of a consanguineous marriage presented with cutaneous manifestations, alopecia, developmental delay, hypotonia with absent neck holding, respiratory problems, and biotinidase deficiency.</p><p><strong>Methods: </strong>Biochemical characterization was performed using tandem mass spectrometry and immunofluorescence enzyme assays. Pathogenic genetic variant was identified by Sanger sequencing of the <i>BTD</i> (biotinidase) gene in a patient and his parents.</p><p><strong>Results: </strong>Biochemical characterization indicated elevated methylmalonylcarnitine/hydroxyisovalerylcarnitine and decreased biotinidase, citrulline, glycine, and ornithine levels, suggesting a profound biotinidase deficiency. Sequencing of <i>BTD</i> gene indicates the presence of a 7-bp deletion and a 3-bp insertion (98-104del7ins3) in a homozygous state, resulting in a change of amino acid from cystine to phenylalanine at the 33rd position, causing a frameshift and premature amino acid termination at the 68th position.</p><p><strong>Conclusions: </strong>A 7-bp deletion and a 3-bp insertion (98-104del7ins3) homozygous variation in the <i>BTD</i> gene segregating in a homozygous recessive manner in the family, causing truncated, nonfunctional biotinidase deficiency in the proband. This is a recurrent mutation and has the potential to be used as a biomarker for screening patients with biotinidase deficiency.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"219-224"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470038","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":"Association of Serum IL-17A Levels and IL-17/IL-17R Gene Variants with Community-Acquired Pneumonia in Iranian Children.","authors":"Leila Sharifie, Maede Jafari, Saeedeh Parvaresh, Maryam Eskandari, Ali Hosseininasab, Maral Choopanizadeh, Mahtab Kalani, Mehdi Kalani","doi":"10.1177/19450265261469740","DOIUrl":"10.1177/19450265261469740","url":null,"abstract":"<p><strong>Background: </strong>Because the IL-17/IL-17 receptor (IL-17R) axis is involved in lung inflammation and genetic variants, such as single nucleotide polymorphisms (SNPs), can affect its function, this study examined the associations between IL-17/IL-17R gene SNPs, serum IL-17A levels, and community-acquired pneumonia (CAP) in Iranian children.</p><p><strong>Methods: </strong>A total of 266 subjects were enrolled in this study, comprising 126 children with CAP and 140 healthy controls. Genetic variants in the IL-17 and IL-17R genes were characterized by allele-specific PCR and PCR restriction fragment length polymorphism, respectively. Concurrently, serum IL-17A concentrations were measured by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>Serum IL-17A levels were significantly higher in patients than in controls (295.8 ± 138.5 pg/mL vs. 40.6 ± 35.3 pg/mL, respectively; <i>p</i> = 0.001). Although the allele and genotype frequencies of IL-17 rs4711998 and IL-17 rs3748067 showed no significant association with CAP, the AA genotype and A allele of IL-17R rs4819554 were significantly more frequent in the patient group. Correlation analysis found no significant association between IL-17 genotypes and serum IL-17A levels. However, a significant positive correlation was observed between IL-17A levels and fever (<i>p</i> = 0.001).</p><p><strong>Conclusion: </strong>The upregulation of IL-17A in patient sera and its correlation with fever support a role for IL-17A in the pathogenesis of CAP. Furthermore, the A allele and AA genotype of IL-17R rs4819554 were identified as potential risk factors for CAP in Iranian children. The lack of a significant association between IL-17 gene variants and serum IL-17A levels may be attributable to the complex regulatory network governing IL-17 production.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"225-232"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470129","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}