Journal of Genetics最新文献_第2页

THPO promoter mutation: a familial study on congenital amegakaryocytic thrombocytopenia. THPO启动子突变：先天性单核细胞血小板减少症的家族性研究。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Reyhaneh Dehghanzad, Roghayeh Rahbar Parvaneh, Maryam Jamshidifar, Zahra Khaffafpour, Roghayeh Rahimi Afzal, Sharareh Kamfar, Bibi Shahin Shamsian, Mohammad Keramatipour

{"title":"THPO promoter mutation: a familial study on congenital amegakaryocytic thrombocytopenia.","authors":"Reyhaneh Dehghanzad, Roghayeh Rahbar Parvaneh, Maryam Jamshidifar, Zahra Khaffafpour, Roghayeh Rahimi Afzal, Sharareh Kamfar, Bibi Shahin Shamsian, Mohammad Keramatipour","doi":"","DOIUrl":"","url":null,"abstract":"Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure syndrome, which is characterized by a severe thrombocytopenia at birth without predictive stigmata and by a risk for progression into aplastic anaemia and myeloid malignancy. While CAMT primarily arises from mutations in the MPL gene, recent discoveries have linked biallelic THPO mutations to some CAMT cases. In addition, loss of function monoallelic mutations in this gene have been identified as causing benign autosomal dominant thrombocytopenia. In this study, we report a case of CAMT linked to a homozygous mutation in the promoter region of THPO (c.-324C>T, NM_000460.4). computational analysis indicates that this mutation suppresses the binding of some essential transcription factors to the THPO promoter. Family segregation analysis shows a significant reduction in platelet counts among carriers of the mutation. Our patient received allogeneic haematopoietic stem cell transplantation (HSCT) from her HLA-matched sister (MSD), who carries the mutation. After allogeneic HSCT, the patient showed 100% full donor chimerism, but 1 year after HSCT, despite full donor chimerism, the patient did not complete recover from platelet count, and she has received romiplostim several times. Understanding the MPL-THPO pathway is vital for managing CAMT, emphasizing the importance of identifying and assessing patients' mutations for tailored treatment.","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093890","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}

引用次数: 0

JAG1 overexpression partially rescues muscle function in a zebrafish model of duchenne muscular dystrophy. 在杜氏肌营养不良斑马鱼模型中，JAG1过表达可部分恢复肌肉功能。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Vishakha Nesari, Suresh Balakrishnan, Upendra Nongthomba

{"title":"JAG1 overexpression partially rescues muscle function in a zebrafish model of duchenne muscular dystrophy.","authors":"Vishakha Nesari, Suresh Balakrishnan, Upendra Nongthomba","doi":"","DOIUrl":"","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration and loss of function due to the absence of dystrophin. In this study, we utilized a zebrafish model with a dmd gene knockout to explore the therapeutic potential of JAG1 overexpression in mitigating DMD-associated muscle dysfunction. Dystrophic zebrafish larvae displayed significant impairments in muscle function, evidenced by reduced swimming abilities, decreased birefringence, and disrupted β-dystroglycan localization, indicative of structural degeneration. Overexpression of JAG1, achieved via plasmid injection, partially restored muscle function, as reflected by improvements in stride length and total swimming distance. However, the structural integrity of slow oxidative muscle fibers remained largely unaffected, with a functional decline from 4 to 8 days post-fertilization (dpf) being more indicative of disease progression than structural changes. These findings suggest that the rescue effect of JAG1 overexpression may not be due to the preservation of slow oxidative fibers but rather through a mechanism that reduces susceptibility to contraction-induced injury. Notably, our study faced limitations related to the control of JAG1 expression levels and tissue specificity. Our results highlight the complexity of DMD pathology, where muscle structure and function do not always correlate, emphasizing the need for refined functional assays to better assess therapeutic outcomes. By incorporating functional recovery assessments at 8-10 dpf, zebrafish models can serve as more predictive preclinical tools, potentially enhancing the translational relevance of findings and reducing risks for patients in clinical trials. This study investigates how increasing the levels of a protein called JAG1 can help improve muscle function in a zebrafish model of DMD. By showing partial recovery of muscle activity, the findings suggest new therapeutic strategies that could potentially slow disease progression and improve patient outcomes.","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440809","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}

引用次数: 0

Analysis of whole-exome data of nonobese NAFLD patients from India reveals association with new markers on functionally relevant genes and pathways. 来自印度的非肥胖NAFLD患者的全外显子组数据分析揭示了与功能相关基因和途径上的新标记的关联。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Arnab Ghosh, Anamita Barik, Rajesh K Rai, Jeffrey D Wall, Abhijit Chowdhury, Parha P Majumder

{"title":"Analysis of whole-exome data of nonobese NAFLD patients from India reveals association with new markers on functionally relevant genes and pathways.","authors":"Arnab Ghosh, Anamita Barik, Rajesh K Rai, Jeffrey D Wall, Abhijit Chowdhury, Parha P Majumder","doi":"","DOIUrl":"","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) occurs in a significant number of nonobese individuals, especially in Asian populations. Many genetic loci are associated with NAFLD. However, no exome-wide analysis of polymorphism data to identify asso- ciations with NAFLD is available for nonobese individuals from Asia. We have sought to fill this gap. With informed consent, we selected individuals from a defined population in India and assessed their liver fat-graded per international recommendations, and their demo- graphic and anthropometric data were collected. A set of 153 individuals were identified with high-grade liver fat. For each of these fatty- liver individuals (cases), two controls of the same sex with no or little liver fat were selected, the age and BMI of each control not exceeding 5 years and 5 kg/m2, respectively, of the case. Whole-genome sequencing was done for each individual. For association analysis, we selected only nonsynonymous germline single-nucleotide polymorphisms (SNPs) in coding regions located on genes expressed in the liver. We removed SNPs and individuals with compromised quality and informativeness. We carried out association analysis in this high-quality data set and validated the results using a novel bootstrap procedure. On the basis of this high-stringency association analysis using exome- wideSNP data on 438 cases and controls, we identified 30 significant SNPs on 24 genes. Of these, 21 SNPs from 17 genes are hitherto unreported. We have determined that most of the significant SNPs are functionally relevant. Pathway analysis revealed that the genes on which these SNPs are located are involved in liver dysfunction.","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093891","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}

引用次数: 0

Gonadal mosaicism and paradoxical phenotype in NEXMIF encephalopathy: a case report of two siblings. 性腺镶嵌和悖论表型在NEXMIF脑病：两个兄弟姐妹的病例报告。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Naik Adarsha, Haseena Sait

引用次数: 0

Understanding the prevalence of germline oncogenic biomarker variants across the Indian population. 了解生殖系致癌生物标志物变异在印度人群中的流行。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Aastha Vatsyayan, Rahul C Bhoyar, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Bani Jolly, Sridhar Sivasubbu, Vinod Scaria

{"title":"Understanding the prevalence of germline oncogenic biomarker variants across the Indian population.","authors":"Aastha Vatsyayan, Rahul C Bhoyar, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Bani Jolly, Sridhar Sivasubbu, Vinod Scaria","doi":"","DOIUrl":"","url":null,"abstract":"Genomic biomarkers are essential aspects of personalized medicine. They offer an opportunity for early detection and appropriate intervention, thereby leading to improved patient outcomes and cost-effective treatment. However, different populations have varied genetic landscapes, and thus, may have unique biomarkers. Here we study the prevalence of mutation-specific oncogenic biomarkers in the Indian population and analyse their presence across disease cohorts. We annotate the IndiGen data obtained from whole genome sequencing of 1029 self-declared healthy Indian individuals with biomarker information obtained from the OncoKB knowledgebase, a repository of evidence-based information about somatic biomarkers and structural alterations in patient tumours. We further establish the utility of this study by analysing these biomarkers across GUaRDIAN, a nationwide multi-cohort database, and MUSTARD, a repository of mutation-specific therapies in cancer. In this study, we discovered 34 biomarker variants of therapeutic actionability across 16 genes linked to 23 unique drugs or drug combinations in 23 unique types of cancer. In all, we have found 52 biomarker variants with 172 different biomarker types including therapeutic, resistance, diagnostic, and prognostic. We establish that nearly 7% of the population were found to be carriers of at least one of the four evidence-based biomarkers. Finally, we also establish the prevalence of 42 biomarker variants across 23 genes in both AD and AR modes of inheritance. We have calculated the prevalence of cancer biomarkers of therapeutic, diagnostic and prognostic value in the globally underrepresented Indian population. The known biomarker landscape so established can be used for clinical advantage to improve patient care. Cancers without corresponding biomarker matches can also be further studied to discover biomarkers unique to Indian populations.","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642757","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}

引用次数: 0

Analysis of tandem repeats in seven telomere-to-telomere primate genomes. 7个端粒-端粒灵长类基因组串联重复序列分析。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Anukrati Sharma, Divya Tej Sowpati

{"title":"Analysis of tandem repeats in seven telomere-to-telomere primate genomes.","authors":"Anukrati Sharma, Divya Tej Sowpati","doi":"","DOIUrl":"","url":null,"abstract":"Tandem repeats (TRs) are highly polymorphic low complexity regions present in all the genomes. The length variation in TRs, particularly that of short TRs (STRs), is associated with several cellular functions such as gene expression and genome organization. In humans, an abnormal expansion of a few STR loci is linked to neurodegenerative diseases. Despite their importance, limitations and gaps in reference genomes prohibit the comprehensive analysis of TRs. Recent advances in high-throughput sequencing technologies have enabled the generation of gapless, telomere-to-telomere (T2T) genomes of humans and other ape species. Here, we report the TR landscape of seven primate T2T genomes, including humans. Our analysis indicates that TRs of 1-100 nucleotide (nt) motifs cover 3.5-6.9% of large primate genomes, with the highest density observed in gorilla (69 kb per Mbp). Large motif size TRs are prevalent and contribute abundantly to higher-order repeats. As an example, we describe a species-specific 32 nt A/T rich motif that contributes to subtelomeric repeats. Finally, we present the motif decomposition and substructure of pentameric repeats in Y chromosomes of six ape species. Our work illutrates the dynamics of TRs in large genomes, and showcases the utility of complete genomes for better understanding the role of low complexity sequences.","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333254","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}

引用次数: 0

Deletion of RAI1 noncoding exons 1-2 causes Smith-Magenis syndrome. RAI1非编码外显子1-2的缺失导致Smith-Magenis综合征。

IF 2.9 4区生物学

Journal of Genetics Pub Date : 2025-01-01

Uri Hamiel, Alina Kurolap, Chofit Chai Gadot, Adi Mory, Anat Bar Shira, Hagit Baris Feldman, Daphna Marom

{"title":"Deletion of RAI1 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":"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 RAI1 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 RAI. To determine whether the deletion of the noncoding exons 1-2 of the RAI1 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 RAI1 mRNA expression. CMA confirmed a de novo 737.8 kbp deletion on 17p11.2, which includes exons 1-2 of RAI1 but spares exons 3 onwards. RT-qPCR analysis on RNA extracted from the patient, father and three unrelated controls revealed that the patient has RAI1 haploinsufficiency. We show that deletion of the RAI1 noncoding exons 1-2, which spares the gene's coding region, causes RAI1 haploinsufficiency by eliminating regulatory elements, including the gene promoter, thus causing SMS and expanding the mutational spectrum of SMS.","PeriodicalId":15907,"journal":{"name":"Journal of Genetics","volume":"104 ","pages":""},"PeriodicalIF":2.9,"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}

引用次数: 0

A novel intron variant in the prolactin gene associated with eggshell weight and thickness with putative alternative splicing patterns in chickens 催乳素基因中的一个新型内含子变异与鸡的蛋壳重量和厚度有关，并具有假定的替代剪接模式

IF 1.5 4区生物学

Journal of Genetics Pub Date : 2024-09-14 DOI: 10.1007/s12041-024-01482-w

Dhafer A. Ali, Nihad Abdul-Lateef Ali, Thamer R. S. Aljubouri, Mohammed Baqur S. Al-Shuhaib

{"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":"Raising Iraqi indigenous chickens (IIC) is restricted by their thin and low eggshell weights. Due to the importance of the prolactin (Prl) gene in regulating a wide range of egg production traits, this study assessed the potential genetic polymorphisms associated with Prl that may influence these traits. The polymorphism was examined in three Prl loci of the IIC breed (n = 120) in comparison with the standard Hyline breed (n = 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 Prl by polymerase chain reaction-single-stranded conformation polymorphism (SSCP) method, only one novel SNP was identified in intron 4, namely 129G > 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 in silico 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.","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}

引用次数: 0

Assessment of the contribution of VDR and VDBP/GC genes in the pathogenesis of celiac disease 评估 VDR 和 VDBP/GC 基因在乳糜泻发病机制中的作用

IF 1.5 4区生物学

Journal of Genetics Pub Date : 2024-09-13 DOI: 10.1007/s12041-024-01480-y

Pratibha Banerjee, Harinder Singh, Priyanka Tiwari, Ajit Sood, Vandana Midha, Gursewak Singh, B K Thelma, Sabyasachi Senapati

{"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":"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 (VDR) 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 (VDBP/GC) using PCR-RFLP were done in 969 subjects including CD cases (n=506) and controls (n=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), P<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 P=0.001. Notably, rs7041-GG, rs4588-CC, and 1F (GC) haplotype of VDBP/GC showed significant association (P<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, P=0.005). The present study highlights the significance of reduced vitamin-D serum level in CD. 1F variant of VDBP 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.","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}

引用次数: 0

A novel missense variant in PNLDC1 associated with nonobstructive azoospermia 与非梗阻性无精子症相关的 PNLDC1 新型错义变体

IF 1.5 4区生物学

Journal of Genetics Pub Date : 2024-08-20 DOI: 10.1007/s12041-024-01478-6

Mouness Rahimian, Masomeh Askari, Najmeh Salehi, Mojtaba Jaafarinia, Mohsen Forouzanfar, Navid Almadani, Andrea Riccio, Mehdi Totonchi

{"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":"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 PNLDC1 (NM_173516:exon9:c.710G>A;p.Gly237Asp). In silico, 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 PNLDC1 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.","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}

引用次数: 0