Journal of rare diseases (Berlin, Germany)最新文献

{"title":"Use of whole genome sequencing to determine the genetic basis of visceral myopathies including Prune Belly syndrome.","authors":"Robert M Geraghty, Sarah Orr, Eric Olinger, Ruxandra Neatu, Miguel Barroso-Gil, Holly Mabillard, Genomics England Research Consortium, Ian Wilson, John A Sayer","doi":"10.1007/s44162-023-00012-z","DOIUrl":"10.1007/s44162-023-00012-z","url":null,"abstract":"<p><strong>Objectives/aims: </strong>The visceral myopathies (VM) are a group of disorders characterised by poorly contractile or acontractile smooth muscle. They manifest in both the GI and GU tracts, ranging from megacystis to Prune Belly syndrome. We aimed to apply a bespoke virtual genetic panel and describe novel variants associated with this condition using whole genome sequencing data within the Genomics England 100,000 Genomes Project.</p><p><strong>Methods: </strong>We screened the Genomics England 100,000 Genomes Project rare diseases database for patients with VM-related phenotypes. These patients were screened for sequence variants and copy number variants (CNV) in <i>ACTG2</i>, <i>ACTA2</i>, <i>MYH11</i>, <i>MYLK</i>, <i>LMOD1</i>, <i>CHRM3</i>, <i>MYL9</i>, <i>FLNA</i> and <i>KNCMA1</i> by analysing whole genome sequencing data. The identified variants were analysed using variant effect predictor online tool, and any possible segregation in other family members and novel missense mutations was modelled using in silico tools. The VM cohort was also used to perform a genome-wide variant burden test in order to identify confirm gene associations in this cohort.</p><p><strong>Results: </strong>We identified 76 patients with phenotypes consistent with a diagnosis of VM. The range of presentations included megacystis/microcolon hypoperistalsis syndrome, Prune Belly syndrome and chronic intestinal pseudo-obstruction. Of the patients in whom we identified heterozygous <i>ACTG2</i> variants, 7 had likely pathogenic variants including 1 novel likely pathogenic allele. There were 4 patients in whom we identified a heterozygous <i>MYH11</i> variant of uncertain significance which leads to a frameshift and a predicted protein elongation. We identified one family in whom we found a heterozygous variant of uncertain significance in <i>KCNMA1</i> which in silico models predicted to be disease causing and may explain the VM phenotype seen. We did not find any CNV changes in known genes leading to VM-related disease phenotypes. In this phenotype selected cohort, <i>ACTG2</i> is the largest monogenic cause of VM-related disease accounting for 9% of the cohort, supported by a variant burden test approach, which identified <i>ACTG2</i> variants as the largest contributor to VM-related phenotypes.</p><p><strong>Conclusions: </strong>VM are a group of disorders that are not easily classified and may be given different diagnostic labels depending on their phenotype. Molecular genetic analysis of these patients is valuable as it allows precise diagnosis and aids understanding of the underlying disease manifestations. We identified <i>ACTG2</i> as the most frequent genetic cause of VM. We recommend a nomenclature change to 'autosomal dominant ACTG2 visceral myopathy' for patients with pathogenic variants in <i>ACTG2</i> and associated VM phenotype<i>s</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material av","PeriodicalId":73925,"journal":{"name":"Journal of rare diseases (Berlin, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9955084","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":"Retrospective analysis of COVID-19 patients developing otherwise rare complications.","authors":"Kevin Stepanek,&nbsp;Pritha Chitagi","doi":"10.1007/s44162-023-00006-x","DOIUrl":"https://doi.org/10.1007/s44162-023-00006-x","url":null,"abstract":"<p><strong>Background: </strong>Over the last 2 years, it has been felt that there was a disproportionate incidence of complications including pneumothorax, pneumomediastinum, and renal disease necessitating dialysis in patients with COVID-19 as compared to patients without COVID-19.</p><p><strong>Methods: </strong>In a retrospective cohort, all patients were admitted to St. Joseph Mercy Oakland Hospital in Pontiac, Michigan, between March 2020 and November 2021. The data collected included age, sex, BMI, length of stay, COVID-19 PCR result, diagnosis of pneumothorax, diagnosis of pneumomediastinum, diagnosis of renal failure, orders for dialysis, and orders for mechanical ventilation.</p><p><strong>Results: </strong>Nine thousand five hundred twenty-two patients are included in this study, with 35.6% (3,392 patients) COVID-19 suspected or confirmed positive and 64.4% (6130 patients) confirmed COVID-19 negative. There were 29 cases of pneumomediastinum and 24 cases of pneumothorax, none of which occurred in intubated patients. The incidence of pneumomediastinum (<i>p</i> = 0.001), CODE BLUE (<i>p</i> = 0.01), and mechanical ventilation (<i>p</i> = 0.001) was significantly higher in the COVID-19 positive/suspected group. There was no significant difference in incidence of pneumothorax (<i>p</i> = 0.294). The incidence of dialysis was significantly higher (<i>p</i> < 0.0001) in the COVID-19 negative group.</p><p><strong>Conclusions: </strong>In review of prior literature and proposed mechanisms, we believe that it was possibly the damage that SARS-CoV-2 inflicts upon lung parenchyma that led to the increased incidence of pneumomediastinum. Given our mixed findings of incidences of pneumomediastinum, pneumothorax, and dialysis, our hope is to remain vigilant to uncover further disease associations and/or complications as more COVID-19 case data becomes available.</p>","PeriodicalId":73925,"journal":{"name":"Journal of rare diseases (Berlin, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9906576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10708972","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":"JORD Editor-in-Chief’s welcome: rare diseases from science to practice","authors":"Neveen A. Soliman","doi":"10.1007/s44162-022-00001-8","DOIUrl":"https://doi.org/10.1007/s44162-022-00001-8","url":null,"abstract":"","PeriodicalId":73925,"journal":{"name":"Journal of rare diseases (Berlin, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42349286","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":"The impact of consanguinity on human health and disease with an emphasis on rare diseases","authors":"G. Temaj, N. Nuhii, J. Sayer","doi":"10.1007/s44162-022-00004-5","DOIUrl":"https://doi.org/10.1007/s44162-022-00004-5","url":null,"abstract":"","PeriodicalId":73925,"journal":{"name":"Journal of rare diseases (Berlin, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42410398","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":"Epidemiology of congenital disorders of glycosylation (CDG)—overview and perspectives","authors":"A. Piedade, R. Francisco, J. Jaeken, P. Sarkhail, S. Brasil, C. Ferreira, T. Rijoff, C. Pascoal, Alexandre Gil, Ana Beatriz Lourenço, Marta Abreu, Mafalda Gomes, P. Videira, V. Reis Ferreira","doi":"10.1007/s44162-022-00003-6","DOIUrl":"https://doi.org/10.1007/s44162-022-00003-6","url":null,"abstract":"","PeriodicalId":73925,"journal":{"name":"Journal of rare diseases (Berlin, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48506605","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":"UMOD and you! Explaining a rare disease diagnosis.","authors":"Holly Mabillard,&nbsp;Eric Olinger,&nbsp;John A Sayer","doi":"10.1007/s44162-022-00005-4","DOIUrl":"https://doi.org/10.1007/s44162-022-00005-4","url":null,"abstract":"<p><p>The precise molecular genetic diagnosis of a rare inherited disease is nearly always a prolonged odyssey. Fortunately, modern molecular testing strategies are allowing more diagnoses to be made. There are many different rare inherited kidney diseases and both the genetic heterogeneity of these conditions and the clinical diversity often leads to confusing nomenclature. Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an example of this. ADTKD, an inherited kidney disease that leads to worsening of kidney function over time, often culminating in end stage kidney disease, accounting for around 2% of this cohort. <i>UMOD</i> is the most common gene implicated in this disorder but there are at least 6 subtypes. At present, there are no specific treatments for ADTKD. Here, we review the current understanding of this condition and provide patient-centred information to allow conceptual understanding of this disease to allow better recognition, diagnosis and management.</p>","PeriodicalId":73925,"journal":{"name":"Journal of rare diseases (Berlin, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9767401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10710967","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}