Application of Clinical Genetics最新文献

{"title":"Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants","authors":"Karen Sánchez, Elizabeth de Mendonca, Xiorama Matute, I. Chaustre, M. Villalón, Howard Takiff","doi":"10.2147/TACG.S78241","DOIUrl":"https://doi.org/10.2147/TACG.S78241","url":null,"abstract":"The mutations in the CFTR gene found in patients with cystic fibrosis (CF) have geographic differences, but there are scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in a group of Venezuelan patients with CF. The 27 exons of the CFTR gene from 110 Venezuelan patients in the National CF Program were amplified and sequenced. A total of 36 different mutations were identified, seven with frequencies greater than 1%: p.Phe508del (27.27%), p.Gly542* (3.18%), c.2988+1G>A (3.18%), p.Arg334Trp (1.36%), p.Arg1162* (1.36%), c.1-8G>C (1.36%), and p.[Gly628Arg;Ser1235Arg](1.36). In 40% of patients, all with a clinical diagnosis of CF, no mutations were found. This report represents the largest cohort of Venezuelan patients with CF ever examined, and includes a wider mutation panel than has been previously studied in this population. Mutations common in Southern European populations predominate, and several new mutations were discovered, but no mutations were found in 40% of the cohort.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"9 1","pages":"33 - 38"},"PeriodicalIF":3.1,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S78241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68481858","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":"Candidate genes of idiopathic pulmonary fibrosis: current evidence and research.","authors":"Wei Zhou, Yaping Wang","doi":"10.2147/TACG.S61999","DOIUrl":"https://doi.org/10.2147/TACG.S61999","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a group of common and lethal forms of idiopathic interstitial pulmonary disease. IPF is characterized by a progressive decline in lung function with a median survival of 2-3 years after diagnosis. Although the pathogenesis of the disease remains unknown, genetic predisposition could play a causal role in IPF. A set of genes have been identified as candidate genes of IPF in the past 20 years. However, the recent technological advances that allow for the analysis of millions of polymorphisms in different subjects have deepened the understanding of the genetic complexity of IPF susceptibility. Genome-wide association studies and whole-genome sequencing continue to reveal the genetic loci associated with IPF risk. In this review, we describe candidate genes on the basis of their functions and aim to gain a better understanding of the genetic basis of IPF. The discovered candidate genes may help to clarify pivotal aspects in the diagnosis, prognosis, and therapies of IPF. </p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"9 ","pages":"5-13"},"PeriodicalIF":3.1,"publicationDate":"2016-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194734","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 individual with cutaneous immunodeficiency and novel 1p36 duplication.","authors":"Alyn D Hatter, David C Soler, Christine Curtis, Kevin D Cooper, Thomas S McCormick","doi":"10.2147/TACG.S90713","DOIUrl":"https://doi.org/10.2147/TACG.S90713","url":null,"abstract":"<p><strong>Introduction: </strong>Crusted or Norwegian scabies is an infectious skin dermatopathology usually associated with an underlying immunodeficiency condition. It is caused when the mite Sarcoptes scabiei infects the skin, and the immune system is unable to control its spread, leading to a massive hyperinfestation with a simultaneous inflammatory and hyperkeratotic reaction. This is the first report of a novel 1p36 duplication associated with a recurrent infection of crusted scabies.</p><p><strong>Case report: </strong>We describe a 34-year-old patient with a cutaneous immunodeficiency characterized by recurrent crusted scabies infestation, diffuse tinea, and recurrent staphylococcal cellulitis, who we suspected had an undiagnosed syndrome. The patient also suffered from mental retardation, renal failure, and premature senescence. A cytogenetic fluorescence in situ hybridization analysis revealed a 9.34 Mb duplication within the short (p) arm of chromosome 1, precisely from 1p36.11 to 1p36.21, with an adjacent 193 kb copy gain entirely within 1p36.11. In addition, chromosome 4 had a 906 kb gain in 4p16.1 and chromosome 9 had a 81 kb copy gain in 9p24.3. Over 100 genes localized within these duplicated regions. Gene expression array revealed 82 genes whose expression changed >1.5-fold compared to a healthy age-matched skin control, but among them only the lipolytic enzyme arylacetamide deacetylase-like 3 was found within the duplicated 1p36 region of chromosome 1.</p><p><strong>Discussion: </strong>Although genetic duplications in the 1p36 region have been previously described, our report describes a novel duplicative variant within the 1p36 region. The patient did not have a past history of immunosuppression but was afflicted by a recurrent case of crusted scabies, raising the possibility that the recurrent infection was associated with the 1p36 genetic duplication.</p><p><strong>Conclusion: </strong>To our knowledge, the specific duplicated sequence between 1p36.11 and p36.21 found in our patient has never been previously reported. We reviewed and compared the clinical, genotyping, and gene microarray results of our patient in order to characterize this novel 1p36 duplication syndrome, which might have contributed to the recurrent scabies infection in this patient.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"9 ","pages":"1-4"},"PeriodicalIF":2.6,"publicationDate":"2016-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676016","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":"The genetics of Charcot–Marie–Tooth disease: current trends and future implications for diagnosis and management","authors":"J. Hoyle, M. Isfort, J. Roggenbuck, D. Arnold, C. hoyle","doi":"10.2147/TACG.S69969","DOIUrl":"https://doi.org/10.2147/TACG.S69969","url":null,"abstract":"Charcot–Marie–Tooth (CMT) disease is the most common hereditary polyneuropathy and is classically associated with an insidious onset of distal predominant motor and sensory loss, muscle wasting, and pes cavus. Other forms of hereditary neuropathy, including sensory predominant or motor predominant forms, are sometimes included in the general classification of CMT, but for the purpose of this review, we will focus primarily on the forms associated with both sensory and motor deficits. CMT has a great deal of genetic heterogeneity, leading to diagnostic considerations that are still rapidly evolving for this disorder. Clinical features, inheritance pattern, gene mutation frequencies, and electrodiagnostic features all are helpful in formulating targeted testing algorithms in practical clinical settings, but these still have shortcomings. Next-generation sequencing (NGS), combined with multigene testing panels, is increasing the sensitivity and efficiency of genetic testing and is quickly overtaking targeted testing strategies. Currently, multigene panel testing and NGS can be considered first-line in many circumstances, although obtaining initial targeted testing for the PMP22 duplication in CMT patients with demyelinating conduction velocities is still a reasonable strategy. As technology improves and cost continues to fall, targeted testing will be completely replaced by multigene NGS panels that can detect the full spectrum of CMT mutations. Nevertheless, clinical acumen is still necessary given the variants of uncertain significance encountered with NGS. Despite the current limitations, the genetic diagnosis of CMT is critical for accurate prognostication, genetic counseling, and in the future, specific targeted therapies. Although whole exome and whole genome sequencing strategies have the power to further elucidate the genetics of CMT, continued technological advances are needed.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"8 1","pages":"235 - 243"},"PeriodicalIF":3.1,"publicationDate":"2015-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S69969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68481709","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}