scholarly journals Clinical RNA sequencing confirms compound heterozygous intronic variants in RYR1 in a patient with congenital myopathy, respiratory failure, neonatal brain hemorrhage, and d‐transposition of the great arteries

2021 ◽  
Author(s):  
Amelle Shillington ◽  
Alonso Zea Vera ◽  
Tanya Perry ◽  
Robert Hopkin ◽  
Cameron Thomas ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Rna Sequencing ◽  
Congenital Myopathy ◽  
Compound Heterozygous ◽  
Brain Hemorrhage ◽  
Neonatal Brain ◽  
Intronic Variants

scholarly journals Complex medical history of a patient with a compound heterozygous mutation in C1QC

Lupus ◽  
2019 ◽  
Vol 28 (10) ◽  
pp. 1255-1260 ◽  
Author(s):  
R Lubbers ◽  
L J J Beaart-van de Voorde ◽  
K van Leeuwen ◽  
M de Boer ◽  
K A Gelderman ◽  
...  
Keyword(s):  
Western Blot ◽  
Medical History ◽  
Rna Sequencing ◽  
Lupus Erythematosus ◽  
Compound Heterozygous Mutation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Classical Pathway ◽  
History Of

Introduction C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. Material and methods Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. Results The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. Discussion The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

scholarly journals Lung transplantation for patients with severe COVID-19

2020 ◽  
Vol 12 (574) ◽  
pp. eabe4282 ◽  
Author(s):  
Ankit Bharat ◽  
Melissa Querrey ◽  
Nikolay S. Markov ◽  
Samuel Kim ◽  
Chitaru Kurihara ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Pulmonary Fibrosis ◽  
Lung Transplantation ◽  
Single Cell ◽  
Rna Sequencing ◽  
Lung Tissue ◽  
Single Molecule ◽  
Sequencing Data ◽  
Native Lung ◽  
Single Cell Rna Sequencing

Lung transplantation can potentially be a life-saving treatment for patients with nonresolving COVID-19–associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with nonresolving COVID-19–associated respiratory failure. We performed single-molecule fluorescence in situ hybridization (smFISH) to detect both positive and negative strands of SARS-CoV-2 RNA in explanted lung tissue from the three patients and in additional control lung tissue samples. We conducted extracellular matrix imaging and single-cell RNA sequencing on explanted lung tissue from the three patients who underwent transplantation and on warm postmortem lung biopsies from two patients who had died from COVID-19–associated pneumonia. Lungs from these five patients with prolonged COVID-19 disease were free of SARS-CoV-2 as detected by smFISH, but pathology showed extensive evidence of injury and fibrosis that resembled end-stage pulmonary fibrosis. Using machine learning, we compared single-cell RNA sequencing data from the lungs of patients with late-stage COVID-19 to that from the lungs of patients with pulmonary fibrosis and identified similarities in gene expression across cell lineages. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival.

Neonatal Brain Hemorrhage: The Role of NonProtein-Bound Iron

2016 ◽  
Vol 06 (02) ◽  
pp. 88-91 ◽  
Author(s):  
Simona Negro ◽  
Maria Tataranno ◽  
Antonino Santacroce ◽  
Carlotta Bracciali ◽  
Mariangela Longini ◽  
...  
Keyword(s):  
Brain Hemorrhage ◽  
Neonatal Brain

Clinical and genetic aspects of hypophosphatasia in Japanese patients

2013 ◽  
Vol 99 (3) ◽  
pp. 211-215 ◽  
Author(s):  
Takeshi Taketani ◽  
Kazumichi Onigata ◽  
Hironori Kobayashi ◽  
Yuichi Mushimoto ◽  
Seiji Fukuda ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Respiratory Failure ◽  
Short Stature ◽  
Clinical Features ◽  
Japanese Patients ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Gradual Improvement ◽  
Clinical Type ◽  
Bone Mineralisation

ObjectiveWe examined the clinical and genetic features of hypophosphatasia (HPP) in Japanese patients. HPP is a rare metabolic bone disorder of bone mineralisation caused by mutations in the liver/bone/kidney alkaline phosphatase (ALPL) gene, which encodes tissue-non-specific alkaline phosphatase isoenzyme. MethodsWe retrospectively investigate the incidence and clinical features of 52 patients with paediatric HPP who were born between 1999 and 2010. Mutations of the ALPL gene were analysed in 31 patients.ResultsThe annual incidence of perinatal lethal HPP (PLH) was estimated to be 2–3/1 000 000 births. The most frequent clinical type was PLH followed by prenatal benign. In addition to bone symptoms, cerebral manifestations were frequently observed including convulsion, mental retardation, deafness and short stature with growth hormone deficiency. Respiratory failure was the most significant predictor of a poor prognosis for PLH. The first and second most frequent mutations in the ALPL gene were c.1559delT and c.T979C (p.F327L), respectively. The c.1559delT homozygous mutation was lethal with respiratory failure. Patients with the p.F327L compound heterozygous mutation had the different non-lethal type with short stature and a gradual improvement in ALP level and bone mineralisation.ConclusionsThe most frequent clinical type was the PLH type with prognosis related to respiratory failure, biochemical/radiological changes and ALPL mutations. Cerebral manifestations frequently occurred. Genotype–phenotype correlations were associated with specific outcomes in the PLH type, whereas different clinical features were associated with the same genotype in the non-lethal type.

scholarly journals Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

2015 ◽  
Vol 22 (10) ◽  
pp. 1214-1238 ◽  
Author(s):  
Tim Lekic ◽  
Damon Klebe ◽  
Roy Poblete ◽  
Paul Krafft ◽  
William Rolland ◽  
...  
Keyword(s):  
Neural Network ◽  
Brain Hemorrhage ◽  
Neonatal Brain ◽  
Vascular Neural Network ◽  
Translational Mechanisms

scholarly journals Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter

2020 ◽  
Vol 6 (3) ◽  
pp. a005074
Author(s):  
Zoltán N. Oltvai ◽  
Eric A. Smith ◽  
Katie Wiens ◽  
Lawrence M. Nogee ◽  
Mark Luquette ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations ◽  
Lipid Transporter

scholarly journals Congenital myopathy associated with the triadin knockout syndrome

Neurology ◽  
2017 ◽  
Vol 88 (12) ◽  
pp. 1153-1156 ◽  
Author(s):  
Andrew G. Engel ◽  
Keeley R. Redhage ◽  
David J. Tester ◽  
Michael J. Ackerman ◽  
Duygu Selcen
Keyword(s):  
Electron Microscopy ◽  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Light And Electron Microscopy ◽  
Deltoid Muscle ◽  
Congenital Myopathy ◽  
Compound Heterozygous

Objective:Triadin is a component of the calcium release complex of cardiac and skeletal muscle. Our objective was to analyze the skeletal muscle phenotype of the triadin knockout syndrome.Methods:We performed clinical evaluation, analyzed morphologic features by light and electron microscopy, and immunolocalized triadin in skeletal muscle.Results:A 6-year-old boy with lifelong muscle weakness had a triadin knockout syndrome caused by compound heterozygous null mutations in triadin. Light microscopy of a deltoid muscle specimen shows multiple small abnormal spaces in all muscle fibers. Triadin immunoreactivity is absent from type 1 fibers and barely detectable in type 2 fibers. Electron microscopy reveals focally distributed dilation and degeneration of the lateral cisterns of the sarcoplasmic reticulum and loss of the triadin anchors from the preserved lateral cisterns.Conclusions:Absence of triadin in humans can result in a congenital myopathy associated with profound pathologic alterations in components of the sarcoplasmic reticulum. Why only some triadin-deficient patients develop a skeletal muscle phenotype remains an unsolved question.

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