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Internal Medicine (Tokyo, Japan) Dec 2021
Topics: Cerebral Hemorrhage; Humans; Porencephaly
PubMed: 34148964
DOI: 10.2169/internalmedicine.7446-21 -
Methods in Cell Biology 2018Collagen IV is a major constituent of basement membranes, specialized form of extracellular matrix that provides a mechanical support for tissues, serves as a polyvalent...
Collagen IV is a major constituent of basement membranes, specialized form of extracellular matrix that provides a mechanical support for tissues, serves as a polyvalent ligand for cell adhesion receptors and as a scaffold for other proteins, and plays a key role in tissue genesis, differentiation, homeostasis, and remodeling. Collagen IV underlies the pathogenesis of several human disorders including Goodpasture's disease, Alport's syndrome, diabetic nephropathy, angiopathy, and porencephaly. While the isolation of the collagen IV molecules from tissues is an ultimate prerequisite for structural and functional studies, it has been always hampered by the protein insolubility due to extensive intermolecular crosslinking and noncovalent associations with other components of basement membranes. In this chapter, we present methods for the isolation of collagen IV fragments from basement membranes or from extracellular matrix deposited by cultured cells, and the recombinant expression alternative. These methods are useful to address the fundamental questions on the role of collagen IV in tissue genesis under the normal and pathological conditions.
Topics: Animals; Basement Membrane; Cells, Cultured; Collagen Type IV; Collagenases; Extracellular Matrix; Humans; Morphogenesis; Pepsin A; Protein Domains; Recombinant Proteins; Solubility
PubMed: 29310777
DOI: 10.1016/bs.mcb.2017.08.010 -
European Journal of Medical Genetics Nov 2020Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those...
Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those patients affected with a monogenic disorder in which an arterial cerebrovascular event or arteriopathy may have preceded any other specific symptom, we aimed to establish and validate a targeted gene panel, and to determine its diagnostic yield and clinical utility. To this end, thirty-eight patients were selected with heterogeneous cryptogenic stroke phenotypes, mostly including multiple and recurrent ischemic or hemorrhagic arterial strokes and porencephalies, variably associated with calcifications, intracranial or systemic steno-occlusive arteriopathies, positive family history, and syndromic conditions. Clinical and neuroradiological data were collected for every patient enrolled in the study, and DNA samples were tested by means of a customized gene panel including 15 genes associated with known genetic diseases related to pediatric stroke. In four patients (10.5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.
Topics: Adolescent; Child; Child, Preschool; Collagen Type IV; Female; Genetic Testing; Humans; Infant; Infant, Newborn; Male; Multidrug Resistance-Associated Proteins; Sequence Analysis, DNA; Stroke
PubMed: 32818659
DOI: 10.1016/j.ejmg.2020.104030 -
Journal of Toxicologic Pathology Jan 2022A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral...
A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral hemisphere and an adhesion area between the cerebral cortex and the skull, which was partially thickened. Additionally, the right optic nerve showed a slight decrease in diameter. Histopathological examination revealed increased glial fibers and collagen fibers, hemosiderin deposition, and an increased number of microglia in the adhesion area, along with a marked reduction of the cerebral parenchyma. In the right eyeball, the retina and optic nerve showed focal atrophy in the nerve fiber layer and inner granular layer to full retinal atrophy and hypoplasia of the myelinated nerve fibers, respectively. Electron microscopic examination revealed hypoplasia of the myelin sheath of nerve fibers in the right optic nerve. This is an extremely rare case of porencephaly and congenital optic nerve hypoplasia, along with independent retinal thinning.
PubMed: 35221503
DOI: 10.1293/tox.2021-0039 -
Yonago Acta Medica Dec 2017Schizencephaly and porencephaly are extremely rare types of cortical dysplasia. Case 1: Prenatal magnetic resonance imaging (MRI) showed wide clefts in the frontal and...
Schizencephaly and porencephaly are extremely rare types of cortical dysplasia. Case 1: Prenatal magnetic resonance imaging (MRI) showed wide clefts in the frontal and parietal lobes bilaterally. On postnatal day 3, MRI T2-weighted images showed multiple hypointensities in the clefts and ventricular walls, suggestive of hemosiderosis secondary to intracranial hemorrhage. Case 2: Prenatal MRI showed bilateral cleft and cyst formation in the fetal cerebrum, as well as calcification and hemosiderosis indicative of past hemorrhage. T2-weighted images showed hypointensities in the same regions as the calcification, corresponding with hemosiderosis due to intracranial hemorrhage on postnatal day 10. Thus, prenatal MRI was useful for diagnosing schizencephaly and porencephaly. Schizencephaly and porencephaly were thought to be due to fetal intracranial hemorrhage, which, in the porencephaly case, may have been related to a mutation of .
PubMed: 29434494
DOI: 10.24563/yam.2017.12.005 -
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 -
Frontiers in Veterinary Science 2023Porencephaly is defined as a fluid-filled cavity of variable size in the brain cortex. It is regarded as a congenital condition and is typically considered a...
INTRODUCTION
Porencephaly is defined as a fluid-filled cavity of variable size in the brain cortex. It is regarded as a congenital condition and is typically considered a developmental or an encephaloclastic defect. Our hypothesis is that postnatal traumatic events in the first few months of life may represent a cause of canine and feline porencephaly that is more common than generally suspected. The aims of this study were to retrospectively investigate porencephaly in a large population of dogs and cats, detect MRI features that might be useful to differentiate postnatal acquired traumatic forms from congenital/perinatal porencephaly, and define the prevalence of seizure activity in porencephalic patients.
MATERIALS AND METHODS
This is a double-center, descriptive, retrospective case series. Databases were searched for cases within a 17-year time span that involve dogs and cats with an MRI-based diagnosis of cerebral cavitary lesions. Animals were included if a complete signalment and an exhaustive MRI of the brain were available. Besides the porencephalic lesions, MRIs of the head were reviewed to detect concomitant musculoskeletal abnormalities.
RESULTS
Thirty-two cases involving nine cats and twenty-three dogs were selected. Of all the cases, 21.9% were aged six years or older at the time of diagnosis. All patients in which the neuroanatomical localization was available showed clinical signs of a prosencephalic disorder. Epileptic seizures were observed in 71.8% of cases. A single porencephalic cavity was found in 78.1% of cases. The most affected cerebral lobe was the parietal lobe ( = 20). The defects involved both the grey and white matter in 78.1% of cases. Twenty cases showed concomitant musculoskeletal abnormalities overlying the porencephalic cavities. Fourteen of twenty cases showed evidence of fractures, of which thirteen showed depression of the calvarium and twelve masticatory muscle abnormalities. Of these, seven of fourteen had a history consistent with a head trauma in the first period of life.
CONCLUSION
The recognition of skull fractures and muscular abnormalities closely associated with the porencephalic cavity may support a diagnosis of a postnatal traumatic origin of porencephaly. Therefore, this study highlights the importance of evaluating musculoskeletal structures in the MRIs of the heads of porencephalic cases.
PubMed: 38125680
DOI: 10.3389/fvets.2023.1302399 -
The Journal of Veterinary Medical... Jul 2015Porencephaly is the congenital cerebral defect and a rare malformation and described few MRI reports in veterinary medicine. MRI features of porencephaly are recognized...
Porencephaly is the congenital cerebral defect and a rare malformation and described few MRI reports in veterinary medicine. MRI features of porencephaly are recognized the coexistence with the unilateral/bilateral hippocampal atrophy, caused by the seizure symptoms in human medicine. We studied 2 dogs and 1 cat with congenital porencephaly to characterize the clinical signs and MRI, and to discuss the associated MRI with hippocampal atrophy. The main clinical sign was the seizure symptoms, and all had hippocampal atrophy at the lesion side or the larger defect side. There is association between hippocampal atrophy or the cyst volume and the severe of clinical signs, and it is suggested that porencephaly coexists with hippocampal atrophy as well as humans in this study.
Topics: Animals; Atrophy; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Hippocampus; Magnetic Resonance Imaging; Male; Porencephaly
PubMed: 25786357
DOI: 10.1292/jvms.14-0359 -
PloS One 2020Optic nerve hypoplasia (ONH) is a congenital malformation with a reduced number of retinal ganglion cell axons in a thin optic nerve. It is a common cause of visual...
Optic nerve hypoplasia (ONH) is a congenital malformation with a reduced number of retinal ganglion cell axons in a thin optic nerve. It is a common cause of visual impairment in children and ONH is associated with neurodevelopmental disorders, pituitary hormone deficiencies, and brain malformations. In most cases, the aetiology is unknown, but both environmental factors and genetic causes have been described. This study aimed to identify genetic variants underlying ONH in a well-characterised cohort of individuals with ONH. We performed array comparative genomic hybridization and whole genome sequencing in 29 individuals with ONH. Rare variants were verified by Sanger sequencing and inheritance was assessed in parental samples. We identified 11 rare single nucleotide variants (SNVs) in ten individuals, including a homozygous variant in KIF7 (previously associated with Joubert syndrome), a heterozygous de novo variant in COL4A1 (previously described in an individual with porencephaly), and a homozygous variant in COL4A2. In addition, one individual harboured a heterozygous variant in OPA1 and a heterozygous variant in COL4A1, both were inherited and assessed as variants of unknown clinical significance. Finally, a heterozygous deletion of 341 kb involving exons 7-18 of SOX5 (associated with Lamb-Schaffer syndrome) was identified in one individual. The overall diagnostic yield of pathogenic or likely pathogenic variants in individuals with ONH using whole genome sequencing was 4/29 (14%). Our results show that there is a genetic heterogeneity in ONH and indicate that genetic causes of ONH are not rare. We conclude that genetic testing is valuable in a substantial proportion of the individuals with ONH, especially in cases with non-isolated ONH.
Topics: Adolescent; Adult; Child; Comparative Genomic Hybridization; Cross-Sectional Studies; Exons; Female; Genetic Heterogeneity; Genetic Testing; Genome, Human; Heterozygote; Humans; Male; Optic Nerve; Optic Nerve Hypoplasia; Pedigree; Phenotype; Polymorphism, Single Nucleotide; Retinal Ganglion Cells; SOXD Transcription Factors; Sweden; Whole Genome Sequencing; Young Adult
PubMed: 32040484
DOI: 10.1371/journal.pone.0228622 -
Journal of Medical Genetics Aug 2021Variants in the type IV collagen gene () cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals...
BACKGROUND
Variants in the type IV collagen gene () cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with variants remain unclear.
METHODS
We examined in 218 individuals with suspected /2-related brain defects. Among those arising from variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.
RESULTS
Pathogenic variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.
CONCLUSIONS
Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and gene testing should be considered when pathogenic variants are strongly suspected.
Topics: Collagen Type IV; Dandy-Walker Syndrome; Female; Humans; Male; Mutation; Pregnancy; Ultrasonography, Prenatal
PubMed: 32732225
DOI: 10.1136/jmedgenet-2020-106896