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Current Opinion in Structural Biology Jun 2019Despite the ubiquity of collagens in the animal kingdom, little is known about the biology of the disaccharide Glc(α1-2)Gal(β1-O) bound to hydroxylysine across... (Review)
Review
Despite the ubiquity of collagens in the animal kingdom, little is known about the biology of the disaccharide Glc(α1-2)Gal(β1-O) bound to hydroxylysine across collagens from sponges to mammals. The extent of collagen glycosylation varies by the types of collagen, with basement membrane collagen type IV being more glycosylated than fibrillar collagens. Beyond true collagens, proteins including collagen domains such as the complement protein 1Q and the hormone adiponectin also feature glycosylated hydroxylysine. Collagen glycosylation is initiated in the endoplasmic reticulum by the galactosyltransferases COLGALT1 and COLGALT2. Mutations in the COLGALT1 gene cause cerebral small vessel abnormality and porencephaly, which are common in collagen type IV deficiency. Beyond the strongly conserved Glc(α1-2)Gal(β1-O) glycan, additional forms of collagen glycosylation have been described in the deep-sea worm Riftia pachyptila and in the giant virus Mimivirus, thereby suggesting that further forms of collagen glycosylation are likely to be identified in the future.
Topics: Animals; Collagen; Disease; Glycosylation; Glycosyltransferases; Humans
PubMed: 30822656
DOI: 10.1016/j.sbi.2019.01.015 -
Genetics in Medicine : Official Journal... Nov 2015Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement... (Meta-Analysis)
Meta-Analysis Review
Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement membrane in many tissues. Since 2005, COL4A1 mutations have been known as an autosomal dominant cause of hereditary porencephaly. COL4A1 and COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, indicated as "COL4A1 mutation-related disorders." Genetic counseling is challenging because of broad phenotypic variation and reduced penetrance. At the Erasmus University Medical Center, diagnostic DNA analysis of both COL4A1 and COL4A2 in 183 index patients was performed between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). The observations in 13 novel families harboring either COL4A1 or COL4A2 mutations prompted us to review the clinical spectrum. We observed recognizable phenotypic patterns and propose a screening protocol at diagnosis. Our data underscore the importance of COL4A1 and COL4A2 mutations in cerebrovascular disease, also in sporadic patients. Follow-up data on symptomatic and asymptomatic mutation carriers are needed for prognosis and appropriate surveillance.
Topics: Alleles; Anterior Eye Segment; Brain; Cerebral Hemorrhage; Cohort Studies; Collagen Type IV; Eye Abnormalities; Eye Diseases, Hereditary; Family; Gene Order; Genetic Association Studies; Genetic Loci; Genotype; Humans; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Mutation; Pedigree; Phenotype; Porencephaly
PubMed: 25719457
DOI: 10.1038/gim.2014.210 -
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 -
Best Practice & Research. Clinical... Jan 2017Cytomegalovirus (CMV) congenital infection affects 0.7% of live births worldwide and is the leading cause of congenital neurological handicap of infectious origin.... (Review)
Review
Cytomegalovirus (CMV) congenital infection affects 0.7% of live births worldwide and is the leading cause of congenital neurological handicap of infectious origin. However, systematic screening for this infection has not been implemented in pregnancy or at birth in any country. This apparent paradox had been justified by persisting gaps in the knowledge of this congenital infection: uncertain epidemiological data, difficulty in the diagnosis of maternal infection, absence of validated prenatal prognostic markers, unavailability of an efficient vaccine and scarcity of data available on the treatment. However, in the last decade, new data have emerged towards better management of this congenital infection, including solid epidemiological data, good evidence for the accuracy of diagnosis of maternal CMV infection and good evidence for the feasibility of predicting the outcome of fetal infection by a combination of fetal imaging and fetal laboratory parameters. There is also some evidence that valaciclovir treatment of mothers carrying an infected fetus is feasible, safe and might be effective. This review provides an update on the evidence for diagnosis, prognosis and treatment of congenital infection in the antenatal period. These suggest a benefit to a proactive approach for prenatal congenital infections.
Topics: Acyclovir; Amniotic Fluid; Antibodies, Viral; Antiviral Agents; Ascites; Cytomegalovirus Infections; DNA, Viral; Female; Fetal Diseases; Humans; Hydrocephalus; Hydrops Fetalis; Immunization, Passive; Immunoglobulin G; Immunoglobulin M; Infectious Disease Transmission, Vertical; Lissencephaly; Microcephaly; Oligohydramnios; Polyhydramnios; Porencephaly; Pregnancy; Pregnancy Complications, Infectious; Seroconversion; Ultrasonography, Prenatal; Valacyclovir; Valine
PubMed: 27923540
DOI: 10.1016/j.bpobgyn.2016.10.005 -
Pediatric Neurology Oct 2023COL4A1/A2 variants affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a cause of fetal and neonatal intracranial hemorrhage,...
BACKGROUND
COL4A1/A2 variants affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a cause of fetal and neonatal intracranial hemorrhage, porencephaly, and schizencephaly. Fetal magnetic resonance imaging (MRI) findings in COL4A1/A2-related disorders are not well characterized.
METHODS
This is a retrospective case series of fetal MRI findings in eight patients with intraparenchymal hemorrhage (IPH) and COL4A1/A2 variants, five of whom have postnatal imaging and clinical follow-up.
RESULTS
IPH was multifocal and bilateral in four of eight patients. IPH involved the frontal lobes in all cases and basal ganglia in six of eight. The median maximum diameter of IPH was 16 mm (range 6 to 65 mm). All patients had ventriculomegaly, and four of eight had intraventricular hemorrhage. Prenatal IPH size correlated clinically with motor outcomes, and none had clinically symptomatic recurrent hemorrhage.
CONCLUSION
COL4A1/A2 variants can present with a spectrum of IPH prenatally, including small and/or unifocal IPH, as well as multifocal and bilateral IPH, involving the frontal lobes and basal ganglia. Given the wide spectrum of IPH severity seen on fetal brain MRI, genetic testing for COL4A1/A2 variants should be considered in all cases of fetal IPH.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Retrospective Studies; Intracranial Hemorrhages; Cerebral Hemorrhage; Fetal Diseases; Collagen Type IV; Magnetic Resonance Imaging
PubMed: 37562171
DOI: 10.1016/j.pediatrneurol.2023.07.008 -
AJNR. American Journal of Neuroradiology Nov 2022The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a...
BACKGROUND AND PURPOSE
The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs.
MATERIALS AND METHODS
A total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities.
RESULTS
Five of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs.
CONCLUSIONS
To our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia.
Topics: Adult; Humans; Adolescent; Telangiectasia, Hereditary Hemorrhagic; Schizencephaly; Polymicrogyria; Retrospective Studies; Arteriovenous Malformations
PubMed: 36265891
DOI: 10.3174/ajnr.A7677 -
Acta Veterinaria Scandinavica Sep 2015Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as... (Review)
Review
Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as a large number of not-yet reported syndromes exist. Foetal infection with certain viruses, including bovine virus diarrhea virus (BVDV), Schmallenberg virus (SBV), blue tongue virus (BTV), Akabane virus (AKAV), or Aino virus (AV), is associated with a range of congenital malformations. It is tempting for veterinary practitioners to diagnose such infections based only on the morphology of the defective offspring. However, diagnosing a virus as a cause of BCMs usually requires laboratory examination and even in such cases, interpretation of findings may be challenging due to lack of experience regarding genetic defects causing similar lesions, even in cases where virus or congenital antibodies are present. Intrauterine infection of the foetus during the susceptible periods of development, i.e. around gestation days 60-180, by BVDV, SBV, BTV, AKAV and AV may cause malformations in the central nervous system, especially in the brain. Brain lesions typically consist of hydranencephaly, porencephaly, hydrocephalus and cerebellar hypoplasia, which in case of SBV, AKAV and AV infections may be associated by malformation of the axial and appendicular skeleton, e.g. arthrogryposis multiplex congenita. Doming of the calvarium is present in some, but not all, cases. None of these lesions are pathognomonic so diagnosing a viral cause based on gross lesions is uncertain. Several genetic defects share morphology with virus induced congenital malformations, so expert advice should be sought when BCMs are encountered.
Topics: Animals; Cattle; Cattle Diseases
PubMed: 26399846
DOI: 10.1186/s13028-015-0145-8 -
Pediatric Neurology Dec 2020Perinatal stroke ranks second only to that of adult stroke in the overall stroke incidence. It is a major contributor to long-term neurological morbidity, which includes... (Review)
Review
Perinatal stroke ranks second only to that of adult stroke in the overall stroke incidence. It is a major contributor to long-term neurological morbidity, which includes cognitive dysfunction, cerebral palsy and seizures. Risk factors for stroke in the perinatal period differ from those in children and tend to be multifactorial. Differences in territorial predilection, response to injury, and stroke evolution exist when compared with childhood and adult stroke, and also among differing gestation age groups in the perinatal period (i.e., extreme preterm versus preterm versus term). The role of imaging is to diagnose stroke, exclude stroke mimics, establish the nature of stroke (arterial versus venous), and aid in prognostication. Magnetic resonance imaging is the mainstay of neuroimaging in perinatal stroke. Advanced imaging techniques such as diffusion tensor imaging and perfusion-weighted imaging are emerging as useful supplements to conventional imaging sequences. Here we describe the neuroimaging of perinatal arterial ischemic stroke with emphasis on imaging techniques, imaging phenotypes, stroke evolution, role of advanced imaging, and differences between stroke in preterm and term neonates. We also briefly describe the emerging role of fetal magnetic resonance imaging in the diagnosis of in utero stroke.
Topics: Fetal Diseases; Humans; Infant, Newborn; Ischemic Stroke; Neuroimaging; Prenatal Diagnosis
PubMed: 33038575
DOI: 10.1016/j.pediatrneurol.2020.08.011 -
American Journal of Obstetrics and... Dec 2020
Review
Topics: Cardiology; Cardiomegaly; Echocardiography; Female; Heart Failure; Humans; Hydrocephalus; Hydrops Fetalis; Neurosurgery; Porencephaly; Pregnancy; Prognosis; Referral and Consultation; Ultrasonography, Prenatal; Vein of Galen Malformations
PubMed: 33168212
DOI: 10.1016/j.ajog.2020.08.181