Molecular Genetics & Genomic Medicine最新文献

{"title":"Loss-of-function polymorphisms in NQO1 are not associated with the development of subacute myelo-optico-neuropathy.","authors":"Hideki Matsumoto, Hideo Sasai, Norio Kawamoto, Masato Katsuyama, Makoto Minamiyama, Satoshi Kuru, Toshiyuki Fukao, Hidenori Ohnishi","doi":"10.1002/mgg3.2470","DOIUrl":"10.1002/mgg3.2470","url":null,"abstract":"<p><strong>Background: </strong>Subacute myelo-optico-neuropathy (SMON) is a neurological disorder associated with the administration of clioquinol, particularly at very high doses. Although clioquinol has been used worldwide, there was an outbreak of SMON in the 1950s-1970s in which the majority of cases were in Japan, prompting speculation that the unique genetic background of the Japanese population may have contributed to the development of SMON. Recently, a possible association between loss-of-function polymorphisms in NQO1 and the development of SMON has been reported. In this study, we analyzed the relationship between NQO1 polymorphisms and SMON in Japan.</p><p><strong>Methods: </strong>We analyzed 125 Japanese patients with SMON. NQO1 loss-of-function polymorphisms (rs1800566, rs10517, rs689452, and rs689456) were evaluated. The allele frequency distribution of each polymorphism was compared between the patients and the healthy Japanese individuals (Human Genomic Variation Database and Integrative Japanese Genome Variation Database), as well as our in-house healthy controls.</p><p><strong>Results: </strong>The frequencies of the loss-of-function NQO1 alleles in patients with SMON and the normal control group did not differ significantly.</p><p><strong>Conclusion: </strong>We conclude that known NQO1 polymorphisms are not associated with the development of SMON.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.","authors":"Panpan Ma, Bingbo Zhou, Qichao Kang, Xue Chen, Xinyuan Tian, Ling Hui, Shengju Hao, Huiyan Wu, Chuan Zhang","doi":"10.1002/mgg3.2434","DOIUrl":"10.1002/mgg3.2434","url":null,"abstract":"<p><strong>Background: </strong>Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family.</p><p><strong>Methods: </strong>We detected and analysed 362 Chinese non-syndromic HL patients by screening of variants in 15 hot spot mutations. Subsequently, 40 patients underwent further whole-exome sequencing (WES) to determine genetic aetiology. The candidate variants were verified using Sanger sequencing. Twenty-three carrier couples with pathogenic variants or likely pathogenic variants chose to proceed with prenatal diagnosis using Sanger sequencing.</p><p><strong>Results: </strong>Among the 362 HL patients, 102 were assigned a molecular diagnosis with 52 different variants in 22 deafness genes. A total of 41 (11.33%) cases with the biallelic GJB2 (OMIM # 220290) gene mutations were detected, and 21 (5.80%) had biallelic SLC26A4 (OMIM # 605646) mutations. Mitochondrial gene (OMIM # 561000) mutations were detected in seven (1.93%) patients. Twenty of the variants in 15 deafness genes were novel. SOX10 (OMIM # 602229), MYO15A (OMIM # 602666) and WFS1 (OMIM # 606201) were each detected in two patients. Meanwhile, OSBPL2 (OMIM # 606731), RRM2B (OMIM # 604712), OTOG (OMIM # 604487), STRC (OMIM # 606440), PCDH15 (OMIM # 605514), LOXHD1 (OMIM # 613072), CDH23 (OMIM # 605516), TMC1 (OMIM # 606706), CHD7 (OMIM # 608892), DIAPH3 (OMIM # 614567), TBC1D24 (OMIM # 613577), TIMM8A (OMIM # 300356), PTPRQ (OMIM # 603317), SALL1 (OMIM # 602218), and GSDME (OMIM # 608798) were each detected in one patient. In addition, as regards one couple with a heterozygous variant of CDH23 and PCDH15, respectively, prenatal diagnosis results suggest that the foetus had double heterozygous (DH) variants of CDH23 and PCDH15, which has a high risk to cause ID/F type Usher syndrome.</p><p><strong>Conclusion: </strong>Our study expanded the spectrum of deafness gene variation, which will contribute to the genetic diagnosis, prenatal diagnosis and the procreation guidance of deaf couple. In addition, the deafness caused by two genes should be paid attention to in the prenatal diagnosis of families with both deaf patients.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.","authors":"Thy Ngoc Nguyen, Giang Son Tran, Hai Duc Hoang, Long Giang Nguyen","doi":"10.1002/mgg3.2468","DOIUrl":"10.1002/mgg3.2468","url":null,"abstract":"<p><strong>Background: </strong>Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly.</p><p><strong>Methods: </strong>Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members.</p><p><strong>Results: </strong>Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. Remarkably, the variant was absent in unaffected individuals within the pedigree, underscoring its association with the polydactyly phenotype. Computational analyses revealed that GLI3 p.Gln494His impacts a residue that is highly conserved across species.</p><p><strong>Conclusion: </strong>The GLI3 zinc finger DNA-binding region is an essential part of the Sonic hedgehog signaling pathway, orchestrating crucial aspects of embryonic development through the regulation of target gene expression. This novel finding not only contributes valuable insights into the molecular pathways governing polydactyly during embryonic development but also has the potential to enhance diagnostic and screening capabilities for this condition in clinical settings.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homozygous TREM2 c.549del; p.(Leu184Serfs*5) variant causing Nasu-Hakola disease in three siblings in a consanguineous Iraqi family: Case report and review of literature.","authors":"Naser Gilani, Fatemeh Bitarafan, Mehmet Ozaslan, Sarah Åsheim, Morteza Heidari, Masoud Garshasbi","doi":"10.1002/mgg3.2476","DOIUrl":"10.1002/mgg3.2476","url":null,"abstract":"<p><strong>Background: </strong>The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and disease-associated microglia (DAM) activation to regulate neuroinflammation, and phagocytosis in the brain. Genetic variations in TREM2 are implicated in neurodegenerative disorders, such as Nasu-hakola disease (NHD), characterized by bone lesions, neuropsychiatric disorders, and early-onset dementia.</p><p><strong>Methods: </strong>We studied 3 siblings with suspected NHD. Whole-exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.</p><p><strong>Results: </strong>We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in TREM2. Our literature review reveals 16 TREM2 mutations causing early-onset dementia and bone lesions.</p><p><strong>Conclusion: </strong>These findings, alongside previous research, elucidate the clinical spectrum of TREM2-related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2-dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2-affected individuals.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive prenatal screening in a pregnant woman with a history of stem cell transplant from a male donor: A case report and literature review.","authors":"Dong Liang, Ying Lin, Chunyu Luo, Hang Li, Ping Hu, Zhengfeng Xu","doi":"10.1002/mgg3.2479","DOIUrl":"10.1002/mgg3.2479","url":null,"abstract":"<p><strong>Background: </strong>As a screening method, inaccuracies in noninvasive prenatal screening (NIPS) exist, which are often attributable to biological factors. One such factor is the history of transplantation. However, there are still limited reports on such NIPS cases.</p><p><strong>Methods: </strong>We report an NIPS case of a pregnant woman who had received a stem cell transplant from a male donor. To determine the karyotype in the woman's original cell, we performed chromosome microarray analysis (CMA) on her postnatal blood and oral mucosa. To comprehensively estimate the cell-free DNA (cfDNA) composition, we further performed standard NIPS procedures on the postnatal plasma. Moreover, we reviewed all published relevant NIPS case reports about pregnant women with transplantation history.</p><p><strong>Results: </strong>NIPS showed a low-risk result for common trisomies with a fetal fraction of 65.80%. CMA on maternal white blood cells showed a nonmosaic male karyotype, while the oral mucosa showed a nonmosaic female karyotype. The proportion of donor's cfDNA in postnatal plasma was 94.73% based on the Y-chromosome reads ratio. The composition of cfDNA in maternal plasma was estimated as follows: prenatally, 13.60% maternal, 65.80% donor, and 20.60% fetal/placental, whereas postnatally, 5.27% maternal and 94.73% donor.</p><p><strong>Conclusions: </strong>This study expanded our understanding of the influence of stem cell transplantation on NIPS, allowing us to optimize NIPS management for these women.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinitis pigmentosa with iris coloboma due to miR-204 gene variant in a Chinese family.","authors":"Zhang Lei, Zhu He-Lin, Wang Hai-Yan, Jia Wei, Wang Ru, Cui Zhi-Li, Wang Qian-Feng","doi":"10.1002/mgg3.2481","DOIUrl":"10.1002/mgg3.2481","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the phenotype and genotype of a Chinese family with autosomal-dominant retinitis pigmentosa (RP) accompanied by iris coloboma.</p><p><strong>Methods: </strong>The proband, a 34-year-old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full-field electroretinography (ffERG). Genetic analyses were conducted through whole-exome sequencing (WES) to screen for variations.</p><p><strong>Results: </strong>Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR-204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members.</p><p><strong>Conclusions: </strong>In this third independent and the first Asian family, the existence of a miR-204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR-204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal-dominant pattern, including in Chinese patients, miR-204 aberrations should be considered.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics of a case of multiple mitochondrial dysfunction syndrome 3.","authors":"Hai Xu, Kai Ma, Yuye Gao, Qijun Song, Chaojin Chen, Xiao Xu, Jiaxi Peng, Yan Sun","doi":"10.1002/mgg3.2485","DOIUrl":"10.1002/mgg3.2485","url":null,"abstract":"<p><strong>Objective: </strong>To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed.</p><p><strong>Methods: </strong>Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen-2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords.</p><p><strong>Results: </strong>The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole-exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions.</p><p><strong>Conclusion: </strong>MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole-exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound heterozygous ABCA12 variants identified in a Chinese patient with congenital ichthyosiform erythroderma: Advancing genotype–phenotype correlations and literature review","authors":"Jia‐Wei Liu, Kexin Guo, Rui Zhang, Rongrong Wang, Dong‐Lai Ma, Xue Zhang","doi":"10.1002/mgg3.2431","DOIUrl":"https://doi.org/10.1002/mgg3.2431","url":null,"abstract":"BackgroundIchthyosis is a common keratotic skin disease with high clinical, etiological and genetic heterogeneity. There are four types of non‐syndromic hereditary ichthyoses, among which autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of recessive Mendelian disorders. ARCI present with different phenotypes and <jats:italic>ABCA12</jats:italic> pathogenic variants have been shown to cause complex ARCI phenotypes, including harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE).MethodsA sporadic male patient, clinically diagnosed with CIE, was enrolled in this study. Exome sequencing was combined with Sanger sequencing to confirm the diagnosis and identify the pathogenic variants. <jats:italic>In silico</jats:italic> predictions were made using multiple software programs, and the identified variants were interpreted using the ACMG guidelines. A review of all literature reported <jats:italic>ABCA12</jats:italic> variants was performed to explore genotype–phenotype correlations.ResultsCompound heterozygous <jats:italic>ABCA12</jats:italic> variants [c.5381+1G&gt;A and c.5485G&gt;C (p.Asp1829His)] (NM_173076) were identified. The two variants were not detected in the public database. c.5381+1G&gt;A is predicted to affect <jats:italic>ABCA12</jats:italic> mRNA splicing and Asp1829 is highly conserved among various species. <jats:italic>In silico</jats:italic> analysis suggested that these two variants were responsible for the phenotype of the patient. Genotype–phenotype correlation analysis showed that biallelic truncation variants and/or exon/amino acid deletions in <jats:italic>ABCA12</jats:italic> are the most common causes of HI. Biallelic missense variants are most common in LI and CIE.ConclusionsThe compound heterozygous <jats:italic>ABCA12</jats:italic> variants caused the CIE phenotype observed in the patient. The spectrum of <jats:italic>ABCA12</jats:italic> pathogenic variants were broaden. Genotype–phenotype correlation analysis provided detailed evidence which can be used in future prenatal diagnosis and can inform the need for genetic counselling for patients with <jats:italic>ABCA12</jats:italic>‐related ARCIs.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insight into FCSK-congenital disorder of glycosylation through a CRISPR-generated cell model.","authors":"Maryam Fazelzadeh Haghighi, Hossein Jafari Khamirani, Jafar Fallahi, Ali Arabi Monfared, Korosh Ashrafi Dehkordi, Seyed Mohammad Bagher Tabei","doi":"10.1002/mgg3.2445","DOIUrl":"10.1002/mgg3.2445","url":null,"abstract":"<p><strong>Background: </strong>FCSK-congenital disorder of glycosylation (FCSK-CDG) is a recently discovered rare autosomal recessive genetic disorder with defective fucosylation due to mutations in the fucokinase encoding gene, FCSK. Despite the essential role of fucokinase in the fucose salvage pathway and severe multisystem manifestations of FCSK-CDG patients, it is not elucidated which cells or which types of fucosylation are affected by its deficiency.</p><p><strong>Methods: </strong>In this study, CRISPR/Cas9 was employed to construct an FCSK-CDG cell model and explore the molecular mechanisms of the disease by lectin flow cytometry and real-time PCR analyses.</p><p><strong>Results: </strong>Comparison of cellular fucosylation by lectin flow cytometry in the created CRISPR/Cas9 FCSK knockout and the same unedited cell lines showed no significant change in the amount of cell surface fucosylated glycans, which is consistent with the only documented previous study on different cell types. It suggests a probable effect of this disease on secretory glycoproteins. Investigating O-fucosylation by analysis of the NOTCH3 gene expression as a potential target revealed a significant decrease in the FCSK knockout cells compared with the same unedited ones, proving the effect of fucokinase deficiency on EGF-like repeats O-fucosylation.</p><p><strong>Conclusion: </strong>This study expands insight into the FCSK-CDG molecular mechanism; to the best of our knowledge, it is the first research conducted to reveal a gene whose expression level alters due to this disease.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a new mutation in the ACTL9 gene in men with unexplained infertility.","authors":"Roya Sinaei, Maryam Eslami, Mohammadreza Dadfar, Alihossein Saberi","doi":"10.1002/mgg3.2448","DOIUrl":"10.1002/mgg3.2448","url":null,"abstract":"<p><strong>Background: </strong>Infertility is defined as the failure to achieve pregnancy after one year of unprotected intercourse within a marital relationship. Approximately 10%-15% of couples worldwide experience infertility issues, with nearly half of these cases attributed to male factors. Among men with unexplained infertility, genetic mutations have been identified as a potential cause. Studies have indicated that mutations affecting the function of the protein encoded by the ACTL9 gene may play a role in male infertility.</p><p><strong>Methods: </strong>The purpose of this research was to identify mutations in the ACTL9 gene associated with male infertility in a sample of 40 infertile men with unknown causes. Genomic DNA extraction and PCR amplification were carried out on samples from each individual. The genetic material was then analyzed using Sanger sequencing, followed by bioinformatics and segregation analysis to determine the potential effects of the observed variations.</p><p><strong>Result: </strong>A novel genetic variant, c.376G>A (p.Glu126Lys), was identified in an infertile male individual, representing a previously unreported finding that was validated through segregation analyses. This specific variant induces a change from glutamate to lysine at the amino acid level by replacing the nucleotide G with A in the genomic DNA sequence, consequently impacting the secondary structure and function of the protein.</p><p><strong>Conclusions: </strong>The conclusive analysis of the procedure indicated that this alteration has the potential to interfere with the process of fertilization, ultimately resulting in the complete failure of fertilization (TFF) and causing male infertility.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}