The Application of Clinical Genetics最新文献

{"title":"A Case of 17q12 Microdeletion Syndrome in a MODY5 Type Diabetes with HNF-1β Gene Mutation Accompanied","authors":"Shuping Zhang, Yamei Ma, Xiu Zang, Hao Heng, Xuekui Liu, Gangshan Peng, Ran Liu, Jun Liang, H. Geng","doi":"10.2147/tacg.s465859","DOIUrl":"https://doi.org/10.2147/tacg.s465859","url":null,"abstract":"","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"14 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141710739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Case of de Novo 2p15 Microdeletion Syndrome with Deletion Covering XPO1 and USP34 Genes Diagnosed in a Child – A Case Report","authors":"G. Ręka, Katarzyna Wojciechowska, Monika Lejman","doi":"10.2147/tacg.s465575","DOIUrl":"https://doi.org/10.2147/tacg.s465575","url":null,"abstract":"","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"25 2‐3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141689086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Analysis of BRCA1 3’UTR Variants Predisposing to Breast Cancer","authors":"Diana Sierra-Díaz, Rodrigo Cabrera, Laura Gonzalez-Vasquez, Mariana Angulo-Aguado, Kevin Llinás-Caballero, Dora Fonseca-Mendoza, Nora Constanza Contreras-Bravo, Carlos Restrepo, Oscar Ortega-Recalde, Adrien Morel","doi":"10.2147/tacg.s444546","DOIUrl":"https://doi.org/10.2147/tacg.s444546","url":null,"abstract":"","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141130756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in Immune Genes and Their Association with Tuberculosis Susceptibility: An Analysis of the African Population","authors":"Wycliff Wodelo, Eddie Wampande, Alfred Andama, David Kateete, Kenneth Ssekatawa","doi":"10.2147/TACG.S457395","DOIUrl":"https://doi.org/10.2147/TACG.S457395","url":null,"abstract":"Abstract Tuberculosis remains a global health concern, with substantial mortality rates worldwide. Genetic factors play a significant role in influencing susceptibility to tuberculosis. This review examines the current progress in studying polymorphisms within immune genes associated with tuberculosis susceptibility, focusing on African populations. The roles of various proteins, including Toll-like receptors, Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Non-Integrin, vitamin D nuclear receptor, soluble C-type lectins such as surfactant proteins A and D, C-type Lectin Domain Family 4 Member E, and mannose-binding lectin, phagocyte cytokines such as Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12, and Interleukin-18, and chemokines such as Interleukin-8, monocyte chemoattractant protein 1, Regulated upon activation, normal T-cell expressed and secreted are explored in the context of tuberculosis susceptibility. We also address the potential impact of genetic variants on protein functions, as well as how these findings align with the genetic polymorphisms not associated with tuberculosis. Functional studies in model systems provide insights into the intricate host-pathogen interactions and susceptibility mechanisms. Despite progress, gaps in knowledge remain, highlighting the need for further investigations. This review emphasizes the association of Single Nucleotide Polymorphisms with diverse aspects of tuberculosis pathogenesis, including disease detection and Mycobacterium tuberculosis infection.","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"49 10","pages":"33 - 46"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preimplantation Genetic Testing for Aneuploidy Could Not Improve Cumulative Live Birth Rate Among 705 Couples with Unexplained Recurrent Implantation Failure","authors":"Yang Liu, Xiangxin Lan, Juanjuan Lu, Qian Zhang, Tingting Zhou, T. Ni, Junhao Yan","doi":"10.2147/tacg.s441784","DOIUrl":"https://doi.org/10.2147/tacg.s441784","url":null,"abstract":"","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139685236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RASopathy Cohort of Patients Enrolled in a Brazilian Reference Center for Rare Diseases: A Novel Familial LZTR1 Variant and Recurrent Mutations.","authors":"Natana Chaves Rabelo,&nbsp;Maria Eduarda Gomes,&nbsp;Isabelle de Oliveira Moraes,&nbsp;Juliana Cantagalli Pfisterer,&nbsp;Guilherme Loss de Morais,&nbsp;Deborah Antunes,&nbsp;Ernesto Raúl Caffarena,&nbsp;Juan Llerena,&nbsp;Sayonara Gonzalez","doi":"10.2147/TACG.S372761","DOIUrl":"https://doi.org/10.2147/TACG.S372761","url":null,"abstract":"<p><strong>Purpose: </strong>Noonan syndrome and related disorders are genetic conditions affecting 1:1000-2000 individuals. Variants causing hyperactivation of the RAS/MAPK pathway lead to phenotypic overlap between syndromes, in addition to an increased risk of pediatric tumors. DNA sequencing methods have been optimized to provide a molecular diagnosis for clinical and genetic heterogeneity conditions. This work aimed to investigate the genetic basis in RASopathy patients through Next Generation Sequencing in a Reference Center for Rare Diseases (IFF/Fiocruz) and implement the precision medicine at a public health institute in Brazil.</p><p><strong>Patients and methods: </strong>This study comprises 26 cases with clinical suspicion of RASopathies. Sanger sequencing was used to screen variants in exons usually affected in the <i>PTPN11</i> and <i>HRAS</i> genes for cases with clinical features of Noonan and Costello syndrome, respectively. Posteriorly, negative and new cases with clinical suspicion of RASopathy were analyzed by clinical or whole-exome sequencing.</p><p><strong>Results: </strong>Molecular analysis revealed recurrent variants and a novel <i>LZTR1</i> missense variant: 24 unrelated individuals with pathogenic variants [<i>PTPN11</i>(11), <i>NF1</i>(2), <i>SOS1</i>(2), <i>SHOC2</i>(2), <i>HRAS</i>(1), <i>BRAF</i>(1), <i>LZTR</i> (1), <i>RAF1</i>(1), <i>KRAS</i>(1), <i>RIT1</i>(1), a patient with co-occurrence of <i>PTPN11</i> and <i>NF1</i> mutations (1)]; familial cases carrying a known pathogenic variant in <i>PTPN11</i> (mother-two children), and a previously undescribed paternally inherited variant in <i>LZTR1</i>. The comparative modeling analysis of the novel <i>LZTR1</i> variant p.Pro225Leu showed local and global changes in the secondary and tertiary structures, showing a decrease of about 1% in the β-sheet content. Furthermore, evolutionary conservation indicated that Pro225 is in a highly conserved region, as observed for known dominant pathogenic variants in this protein.</p><p><strong>Conclusion: </strong>Bringing precision medicine through NGS towards congenital syndromes promotes a better understanding of complex clinical and/or undiagnosed cases. The National Policy for Rare Diseases in Brazil emphasizes the importance of incorporating and optimizing diagnostic methodologies in the Unified Brazilian Health System (SUS). Therefore, this work is an important step for the NGS inclusion in diagnostic genetic routine in the public health system.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"153-170"},"PeriodicalIF":3.1,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/34/tacg-15-153.PMC9595068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40429542","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":"Prenatal Sonographic Features of Rare Chromosome 13 Aberrations.","authors":"Hanna Moczulska,&nbsp;Michal Pietrusinski,&nbsp;Marcin Serafin,&nbsp;Beata Skoczylas,&nbsp;Piotr Sieroszewski,&nbsp;Maciej Borowiec","doi":"10.2147/TACG.S370163","DOIUrl":"https://doi.org/10.2147/TACG.S370163","url":null,"abstract":"<p><strong>Objective: </strong>Trisomy 13 is one of the most common chromosome aberrations diagnosed in the prenatal period, and is associated with some specific dysmorphic features. Rare chromosome 13 aberrations other than trisomy 13 may cause other fetal abnormalities. The aim of the study was to analyze cases with those rare chromosome 13 aberrations.</p><p><strong>Methods: </strong>We analyzed all prenatal tests performed in the Department of Clinical Genetics of the Medical University of Lodz from 2016 to 2021 to find all chromosome 13 aberrations.</p><p><strong>Results: </strong>The most common aberration of chromosome 13 was a simple trisomy 13 (n = 16). We found five rare chromosome 13 aberrations other than simple chromosome 13 trisomy: mosaic trisomy 13 mos 47,XX,+13[11]/46,XX[10], mosaic monosomy 13 mos 46,XY,-13,+mar[9]/46,XY[31], duplication 13q21.1-q31, deletion 13q34 and deletion 13q31.1-q34. The deletion 13q31.1-q34 occurred in monochorionic diamniotic twin pregnancy.</p><p><strong>Conclusion: </strong>Rare aberrations accounted for 24% of all chromosome 13 aberrations. Cases with mosaic monosomy of chromosome 13 and microdeletion 13q had similar abnormalities of the external genitalia and facial dysmorphia. The case with duplication 13q was very similar to the clinical features of chromosome 13 trisomy. Mosaic trisomy 13 can occur without any accompanying anatomical defects.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"145-151"},"PeriodicalIF":3.1,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/68/tacg-15-145.PMC9541672.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33497360","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":"Three-Decade Successive Establishment of Care for Women/Girls from Families with Haemophilia.","authors":"Ampaiwan Chuansumrit,&nbsp;Werasak Sasanakul,&nbsp;Nongnuch Sirachainan,&nbsp;Suttikarn Santiwatana,&nbsp;Praguywan Kadegasem,&nbsp;Pakawan Wongwerawattanakoon,&nbsp;Noppawan Tungbubpha,&nbsp;Juthamard Chantaraamporn","doi":"10.2147/TACG.S381683","DOIUrl":"https://doi.org/10.2147/TACG.S381683","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to report a 3-decade successive establishment of care for women/girls from families with haemophilia.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 462 women/girls from 243 families from 1987 to 2021.</p><p><strong>Results: </strong>Combining phenotypic analysis of coagulation factor and genotypic analysis of either linkage analysis or mutation detection confirmed the status of all obligate haemophilia carriers (A118, B19). For potential carrier, 159 proven carriers (A130, B29) and 146 noncarrier status (A126, B20) were diagnosed except 20 potential carriers (A16, B4). Only 54 prenatal diagnoses were requested resulting in normal males (n = 21), males with haemophilia A (n = 12) and females with either normal or carrier status (n = 21). Additionally, 40 women/girls with haemophilia carrier received a diagnosis of severe haemophilia A with Turner's syndrome (n = 2) and mild haemophilia (A31, B7). The skewed X-chromosome inactivation of the nonmutant factor VIII/IX carrying X-chromosome of 8% (2/25) was found in mild haemophilia. Factor concentrate and desmopressin are prescribed for these affected women/girls. The response of women/girls with either haemophilia carrier or haemophilia was amazement with their religious beliefs and cultural acceptance.</p><p><strong>Conclusion: </strong>Appropriate care for women/girls from families with haemophilia concerning diagnosis and management of haemophilia and carrier has been successively established.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"133-143"},"PeriodicalIF":3.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/11/tacg-15-133.PMC9533780.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33497362","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":"Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy Number Variants in <i>ADGRL3</i> (<i>LPHN3</i>) and Two Pseudogenes.","authors":"Martin H Maurer,&nbsp;Anja Kohler,&nbsp;Melanie Hudemann,&nbsp;Jerome Jüngling,&nbsp;Saskia Biskup,&nbsp;Martin Menzel","doi":"10.2147/TACG.S361239","DOIUrl":"https://doi.org/10.2147/TACG.S361239","url":null,"abstract":"<p><p>We report the finding of two copy number variants (CNVs) in a 12-year-old boy presenting both with autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Clinical features included aggressive behavior, mood instability, suicidal statements, repetitive and restrictive behavior, sensitivity to noise, learning problems and dyslexia, though no intellectual disability was present. Using array-based comparative genomic hybridization (array-CGH), we identified two CNVs, both triplex duplications of 324 kb on 3p26.3, and 284 kb on 4q13.1, respectively. One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled receptor L3 (<i>ADGRL3</i>, former name: latrophilin-3, <i>LPHN3</i>), the other on chromosome 3p26.3 in the region of the two pseudogenes <i>AC090043.1</i> and <i>RPL23AP39</i>. The patient described in the present study showed increased symptoms under methylphenidate treatment but responded positively to 3 mg per day of the atypical neuroleptic drug aripiprazole. To our knowledge, this is the first report of a CNV in the <i>ADGRL3</i> gene and its first association with ASD in humans.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"125-131"},"PeriodicalIF":3.1,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/d2/tacg-15-125.PMC9447451.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33454924","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":"ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy.","authors":"Alyssa M Volmrich,&nbsp;Lauren M Cuénant,&nbsp;Irman Forghani,&nbsp;Sharon L Hsieh,&nbsp;Lauren T Shapiro","doi":"10.2147/TACG.S359479","DOIUrl":"https://doi.org/10.2147/TACG.S359479","url":null,"abstract":"<p><p>Pathogenic variants in the ABCD1 gene on the X chromosome may result in widely heterogenous phenotypes, including adrenomyeloneuropathy (AMN). Affected males typically present in their third or fourth decade of life with progressive lower limb weakness and spasticity, and may develop signs and symptoms of adrenal insufficiency and/or cerebral demyelination. Heterozygous females may be asymptomatic, but may develop a later-onset and more slowly progressive spastic paraparesis. In this review, we describe the clinical presentation of AMN, as well as its diagnosis and management. The role of rehabilitative therapies and options for management of spasticity are highlighted.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"111-123"},"PeriodicalIF":3.1,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/8b/tacg-15-111.PMC9381027.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40709124","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}