Vol 4-1 Mini Review

Spectrum of Lung and Cardiovascular Diseases in Association with Pulmonary Interstitial Glycogenosis

Rose Chami*

Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

“Pulmonary Interstitial Glycogenosis (PIG) associated with a spectrum of neonatal pulmonary disorders”, reported by Cutz et al represents one of the largest series published to date. The report included twenty-eight cases of lung or cardiac disorders with coincident diffuse, patchy, or focal PIG reviewed in Division of Pathology, The Hospital for Sick Children. The authors focused on reporting a spectrum of disorders associated with PIG and described four clinicopathological subgroups including imaging, ultrastructural findings, and clinical outcome. The present paper highlights the main findings reported by Cutz et al, and a review of literature is also presented.

DOI: 10.29245/2572-9411/2018/1.1170 View / Download Pdf View Full Text
Vol 4-1 Research Article

Genetic Landscape of aHUS: A Comprehensive Analysis of Genetic Variants Reported in The Literature

Rui-Ru Ji1*, Tatiana Serebriyskaya2,3, Natalia Kuzkina2,3

1Alexion Pharmaceuticals, Inc., 121 Seaport Boulevard, Boston, MA 02210, USA

2EPAM Systems, 22/2 Zastavskaya Street, MegaPark, 196084, Saint-Petersburg, Russia

3Moscow Institute of Physics and Technology, School of Biological and Medical Physics, 9 Institutskiy per., Dolgoprudny, 141701, Moscow, Russia

Genetic information provides important guidance for long-term management of patients with atypical hemolytic uremic syndrome (aHUS), an extremely rare disease that primarily affects a patient’s kidney. To better understand the phenotypic impact of variants identified in aHUS patients, we systematically mined the National Library of Medicine database for case studies of aHUS patients with identifiable genetic variants. Allelic variants from 10 genes (C3, CFB, CFH, CFI, CFHR1, CFHR3, CFHR5, DGKE, CD46/MCP, and THBD) associated with aHUS were collected from 1652 patients. We analyze the enrichment of genetic variants in this “literature cohort” compared with a reference population, the Genome Aggregation Database (gnomAD). We also used a number of tools to predict the pathogenicity of the variants, attempting to reconcile all the results using the protein structure and conservation data. In total, we identified 447 unique genetic variants: 301 of these were not present in the gnomAD database and thus have “moderate” evidence of pathogenicity; 33 variants have “strong” evidence of pathogenicity by enrichment analysis. This study showcases an in silico framework that patient data aggregation and a large scale sequencing database provided a novel opportunity to understand genotype-phenotype associations in aHUS. This framework can be efficiently applied to other rare diseases where data are sparse to help improve the diagnosis and management of these patients.

aHUS: atypical hemolytic uremic syndrome; gnomAD: Genome Aggregation Database; CD46/MCP: cluster of differentiation 46/membrane cofactor protein; CFH: complement factor H; CFI: complement factor I; CFB: complement factor B; C3: complement component 3; ACMG: American College of Medical Genetics; AF: allele frequency; CFHR1: complement factor H-related protein 1; CFHR3: complement factor H-related protein 3; CFHR5: complement factor H-related protein 5; DGKE: diacylglycerol kinase epsilon; THBD: thrombomodulin; MEDLINE: Medical Literature Analysis and Retrieval System Online; VEP: variant effect predictor; SIFT: sorts intolerant from tolerant substitutions; PROVEAN: protein variation effect analyzer; FATHMM: functional analysis through Hidden Markov Models

DOI: 10.29245/2572-9411/2018/1.1168 View / Download Pdf View Full Text
Vol 4-1 Case Report

Aggressive Angiomyxoma: Only Time Will Tell

Saika Amreen, Yaqoob Wani, Yawar Yaseen, Arshad Parray, Tariq A. Gojwari

Dept. Of Radiodiagnosis & Imaging, SKIMS, Soura, Srinagar, Jammu and Kashmir, India

A 38-year-old primigravida delivered a healthy baby via cesarean section. The patient complained of vague abdominal discomfort a few weeks after surgery. Though blood work was unremarkable, an ultrasound revealed a deep pelvic hypoechoic collection. Patient was afebrile and blood work was unremarkable for infectious etiology. Hemoglobin was normal. The patient was otherwise healthy. This was 6 years ago. The lesion still persists.

DOI: 10.29245/2572-9411/2018/1.1165 View / Download Pdf View Full Text