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Radiology Case Reports Jan 2020Prothrombotic conditions are known risk factors for porencephalic cyst formation and cerebral vein thrombosis. Intracerebral hemorrhage is a potential complication of a...
Prothrombotic conditions are known risk factors for porencephalic cyst formation and cerebral vein thrombosis. Intracerebral hemorrhage is a potential complication of a cerebral vein thrombosis. Porencephaly is a risk factor for intracerebral hemorrhage and cerebral vein thrombosis formation. We present the case of an adult patient with a past medical history of epilepsy and congenital porencephalic cyst with de novo mutation of the COL4A1 gene who presented for episodes of generalized tonic-clonic seizure after a substantial symptom-free period. A brain CT scan showed an intracerebral hemorrhage with porencephalic cyst and superior sagittal sinus thrombosis despite negative thrombophilia work-up. A CT perfusion study, CT angiography, and brain MRI confirmed the diagnosis. The cause-and-effect relationship between porencephalic cysts, cerebral venous thrombosis, and intracerebral hemorrhage is still not clear in the literature.
PubMed: 31762865
DOI: 10.1016/j.radcr.2019.10.028 -
Journal of AAPOS : the Official... Dec 2019
Topics: Cataract; Collagen Type IV; Humans; Infant; Mutation; Ophthalmology; Porencephaly
PubMed: 31580895
DOI: 10.1016/j.jaapos.2019.09.004 -
Canadian Journal of Ophthalmology.... Oct 2019
Topics: Abnormalities, Multiple; Female; Hemianopsia; Humans; Magnetic Resonance Imaging; Middle Aged; Occipital Lobe; Porencephaly; Tomography, Optical Coherence; Visual Acuity; Visual Fields
PubMed: 31564367
DOI: 10.1016/j.jcjo.2019.01.012 -
Brain & Development Jan 2020COL4A1-related disorder is recognized as a systemic disease because the alpha 1 chain of type IV collagen, encoded by COL4A1, is essential for basement membrane...
COL4A1-related disorder is recognized as a systemic disease because the alpha 1 chain of type IV collagen, encoded by COL4A1, is essential for basement membrane stability. However, muscular manifestations related to this disorder are rarely reported. We report the case of a 2-year-old boy with porencephaly, who harbored a de novo COL4A1 mutation of c.1853G > A, p. (Gly618Glu) and exhibited recurrent rhabdomyolysis with viral or bacterial infections. Moreover, he developed obstructive hypertrophic cardiomyopathy which required surgical intervention. Skeletal muscle biopsy revealed findings compatible with fiber-type disproportion. Ultrastructural study demonstrated the similar findings previously reported in mice with Col4a1 mutation including collagen disarray and reduction of electron density in the basement membrane of capillary endothelial cells and muscle fibers. Dilated endoplasmic reticulum in the capillary endothelial cells is also noted. This report adds another disease spectrum of COL4A1 mutation which include porencephaly, hypertrophic cardiomyopathy, rhabdomyolysis and fiber-type disproportion.
Topics: Cardiomyopathy, Hypertrophic; Child, Preschool; Collagen Type IV; Humans; Male; Muscle, Skeletal; Mutation; Porencephaly; Rhabdomyolysis
PubMed: 31540749
DOI: 10.1016/j.braindev.2019.09.001 -
Journal of AAPOS : the Official... Dec 2019
Topics: Brain Diseases; Cataract; Collagen Type IV; Humans; Infant; Mutation; Porencephaly
PubMed: 31525464
DOI: 10.1016/j.jaapos.2019.07.002 -
Acta Virologica 2019Schmallenberg virus (SBV), a neurotropic member of the genus Orthobunyavirus, infects ruminants and causes neurological lesions and fetal malformations including...
Schmallenberg virus (SBV), a neurotropic member of the genus Orthobunyavirus, infects ruminants and causes neurological lesions and fetal malformations including cerebellar hypoplasia, hydranencephaly, and porencephaly. The aim of this study is to establish intracerebral (i.c.) infection of SBV in newborn BALB/c mice and to investigate some of the transcription factors in brain. For this aim, brain samples of newborn BALB/c mice which were infected with SBV i.c. were analyzed by plaque titration and real-time RT-PCR for T-bet, Gata3, RoRγt, Foxp3 and Eomes mRNA levels. Study results showed that SBV can replicate in BALB/c mice brain and cause death of newborn mice with generation of infectious viral particles. Analyses of transcription factor mRNA levels indicated up-regulation of T-bet, Gata3, RoRγt, Foxp3 and down-regulation of Eomes. In this report, we introduce preliminary data of T cell transcription factors affected by SBV infection of BALB/c mice. Keywords: Eomes; Foxp3; Gata3; RoRγt; Schmallenberg virus; T-bet.
Topics: Animals; Animals, Newborn; Brain; Bunyaviridae Infections; Gene Expression Regulation; Mice; Mice, Inbred BALB C; Orthobunyavirus; RNA, Messenger; Ruminants; Transcription Factors; Virus Replication
PubMed: 31507194
DOI: 10.4149/av_2019_306 -
Biology Open Aug 2019The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise the phenotype of embryos stemming...
The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise the phenotype of embryos stemming from mouse lines, which produce embryonically lethal offspring. Our study aims to provide detailed phenotype descriptions of homozygous mutants produced in DMDD and harvested at embryonic day 14.5. This shall provide new information on the role plays in organogenesis and demonstrate the capacity of the DMDD database for identifying models for researching inherited disorders. The DMDD mutants survived organogenesis and thus revealed the full spectrum of organs and tissues, the development of which depends on encoded proteins. They showed defects in the brain, cranial nerves, visual system, lungs, endocrine glands, skeleton, subepithelial tissues and mild to severe cardiovascular malformations. Together, this makes the DMDD line a useful model for identifying the spectrum of defects and for researching the mechanisms underlying autosomal dominant porencephaly 2 (OMIM # 614483), a rare human disease. Thus we demonstrate the general capacity of the DMDD approach and webpage as a valuable source for identifying mouse models for rare diseases.
PubMed: 31331924
DOI: 10.1242/bio.042895 -
Human Genetics Oct 2019Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The...
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The genetic locus containing COL4A1 (13q33-34) has been implicated in vesicoureteral reflux (VUR), but mutations in COL4A1 have not been reported in CAKUT. We hypothesized that COL4A1 mutations cause CAKUT in humans. We performed whole exome sequencing (WES) in 550 families with CAKUT. As negative control cohorts we used WES sequencing data from patients with nephronophthisis (NPHP) with no genetic cause identified (n = 257) and with nephrotic syndrome (NS) due to monogenic causes (n = 100). We identified a not previously reported heterozygous missense variant in COL4A1 in three siblings with isolated VUR. When examining 549 families with CAKUT, we identified nine additional different heterozygous missense mutations in COL4A1 in 11 individuals from 11 unrelated families with CAKUT, while no COL4A1 mutations were identified in a control cohort with NPHP and only one in the cohort with NS. Most individuals (12/14) had isolated CAKUT with no extrarenal features. The predominant phenotype was VUR (9/14). There were no clinical features of the COL4A1-related disorders (e.g., HANAC syndrome, porencephaly, tortuosity of retinal arteries). Whereas COL4A1-related disorders are typically caused by glycine substitutions in the collagenous domain (84.4% of variants), only one variant in our cohort is a glycine substitution within the collagenous domain (1/10). We identified heterozygous COL4A1 mutations as a potential novel autosomal dominant cause of CAKUT that is allelic to the established COL4A1-related disorders and predominantly caused by non-glycine substitutions.
Topics: Alleles; Amino Acid Substitution; Collagen Type IV; Computational Biology; Congenital Abnormalities; DNA Mutational Analysis; Databases, Genetic; Evolution, Molecular; Female; Genetic Association Studies; Genetic Loci; Genomics; Heterozygote; Humans; Kidney; Kidney Diseases, Cystic; Male; Mutation; Nephrotic Syndrome; Phenotype; Urinary Tract; Web Browser; Exome Sequencing
PubMed: 31230195
DOI: 10.1007/s00439-019-02042-4 -
Journal of Critical Care Medicine... Apr 2019Patient-controlled analgesia with morphine is routinely used for postoperative pain management. Due to the safety profiles of the technique, which are patient/disease...
INTRODUCTION
Patient-controlled analgesia with morphine is routinely used for postoperative pain management. Due to the safety profiles of the technique, which are patient/disease related or technique/equipment related, severe respiratory depression requiring opioid antagonists or airway management are uncommon.
CASE PRESENTATION
The case of a patient with right colon carcinoma who was operated on for hemicolectomy under general anaesthesia and who presented with apnoea, after postoperatively receiving an initial bolus of 1mg of morphine. A large post-traumatic porencephalic cyst of the left brain hemisphere, previously undiagnosed, was found on the computed tomography scan. We excluded human errors, technique and equipment factors, and the patient did not have any other predisposing conditions like sleep apnoea, obesity, recent head injury or concurrent use of other sedatives. Previously the patient had been entirely asymptomatic, and her increased susceptibility to respiratory depression was the only clinical manifestation of porencephaly.
CONCLUSION
Adult acquired porencephaly is seldom reported in the literature, clinical manifestations depending on the location and size of the cyst. In the present reported case, increased susceptibility to low-dose opioids might be associated with the structural and functional reorganisation of the brain after head trauma with the occurrence of the porencephalic cyst of the brain.
PubMed: 31161144
DOI: 10.2478/jccm-2019-0011 -
Journal of Comparative Pathology May 2019A 4-month-old puppy died after showing intracranial signs a few days after a suspected viral enteritis. Grossly, the right cerebral hemisphere had a large irregular...
A 4-month-old puppy died after showing intracranial signs a few days after a suspected viral enteritis. Grossly, the right cerebral hemisphere had a large irregular cavity external to the internal capsule. Histopathological examination revealed a cystic lesion in the right hemisphere and non-suppurative inflammation of the diencephalon and periaqueductal nervous tissue. Porencephaly associated with periventricular non-suppurative encephalitis was diagnosed. A nested polymerase chain reaction (PCR) identified the presence of parvovirus DNA in the brain and real-time PCR typed this as canine parvovirus (CPV) type 2a. Immunohistochemistry revealed the presence of CPV antigen in the cytoplasm of scattered cells in the subependymal layers and choroid plexus epithelium. The porencephaly was not associated with inflammatory lesions or CPV antigen and was considered to have preceded the neurological signs. In contrast, the detection of CPV antigen in the subependymal layers and choroid plexus epithelium supported the association of this virus with the periventricular encephalitis.
Topics: Animals; Dog Diseases; Dogs; Encephalitis, Viral; Female; Parvoviridae Infections; Parvovirus, Canine; Porencephaly
PubMed: 31159946
DOI: 10.1016/j.jcpa.2019.03.005