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Transactions of the American... 1995We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain...
PURPOSE
We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain anomalies include cortical dysgenesis, lissencephaly, porencephaly, cerebellar and corpus callosum hypoplasia. We describe six exemplar cases.
METHODS
Scotopic and photopic ERGs adherent to international standards were performed as well as photopic ERGs to long-duration stimuli. CT or MRI studies were also done. The ERGs were compared to age-matched normal control subjects.
RESULTS
ERG changes include reduced amplitude b-waves to blue and red stimuli under scotopic testing conditions. Implicit times were often delayed. The photopic responses also showed reduced amplitude a- and b-waves with implicit time delays. The long-duration photopic ERG done in one case shows attenuation of both ON- and OFF-responses.
CONCLUSIONS
Common underlying developmental genetic or environmental unifying casualties are speculated to be at fault in causing these cases of associated retinal and brain abnormalities. No single etiology is expected. Multiple potential causes acting early in embryogenesis effecting neuronal induction, migration and differentiation are theorized. These occur at a time when brain and retinal cells are sufficiently undifferentiated to be similarly effected. We call these cases examples of Brain Retina Neuroembryodysgenesis (BRNED). Homeobox and PAX genes with global neuronal developmental influences are gene candidates to unify the observed disruption of brain and retinal cell development. The ERG can provide a valuable clinical addition in understanding and ultimately classifying these disorders.
Topics: Brain; Child, Preschool; Dark Adaptation; Electroretinography; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Optic Nerve; Photoreceptor Cells; Retina; Retinal Diseases; Tomography, X-Ray Computed
PubMed: 8719676
DOI: 10.1016/s0002-9394(14)70553-7 -
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 -
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 -
Human Genome Variation 2018Porencephaly and schizencephaly are congenital brain disorders that can be caused by mutations, though the underlying mechanism and developmental processes are poorly...
Porencephaly and schizencephaly are congenital brain disorders that can be caused by mutations, though the underlying mechanism and developmental processes are poorly understood. Here, we report a patient with schizencephaly, detected by fetal ultrasonography and fetal magnetic resonance imaging, with a de novo novel mutation in (c.2645_2646delinsAA, p.Gly882Glu). Our results suggest that the onset of damage that potentially results in schizencephaly occurs mid-pregnancy.
PubMed: 29760938
DOI: 10.1038/s41439-018-0005-y -
Developmental Medicine and Child... Jun 1997The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan...
The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan in 1993 and 1994. The relation was studied between the patients' gestational age at birth and their MRI findings, including the severity of periventricular leukomalacia (PVL) seen on MRI. In 119 of these patients, the CP was thought to be due to acquired, destructive brain injury. PVL was seen in 90 and posthemorrhagic porencephaly in 11. These preterm-type brain injuries were observed often in patients who had been born preterm but were also seen in those born at term. Fullterm-type border-zone infarct, bilateral basal ganglia-thalamic lesion, subcortical leukomalacia, and multicystic encephalomalacia were seen in 9, 14, 7, and 3 patients, respectively; these term-type brain injuries were observed only in patients born at or near term. Of the patients with PVL, 90% had been born preterm. Severe PVL was common in the patients whose gestational ages at birth were between 25 and 32 weeks; all patients with PVL who had been born at term had only mild PVL. The authors concluded that MRI findings for patients with spastic CP are closely correlated with gestational age.
Topics: Adolescent; Adult; Basal Ganglia; Brain; Cerebral Hemorrhage; Cerebral Palsy; Child; Child, Preschool; Gestational Age; Humans; Hypoxia; Infant; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Muscle Spasticity; Severity of Illness Index; Thalamus
PubMed: 9233359
DOI: 10.1111/j.1469-8749.1997.tb07447.x -
Human Genome Variation Nov 2020Genetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients...
Genetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients (21%). All patients were complicated with congenital malformations of the brain, such as porencephaly or schizencephaly. In these patients, hemolysis became less severe within 2 months after birth, and red cell transfusion was no longer required after 50 days, whereas chronic hemolysis continued.
PubMed: 33298904
DOI: 10.1038/s41439-020-00130-w -
Cureus Jan 2024[This retracts the article DOI: 10.7759/cureus.19623.].
[This retracts the article DOI: 10.7759/cureus.19623.].
PubMed: 38274581
DOI: 10.7759/cureus.r97 -
BMC Medical Genetics Aug 2014Almost one-third of congenital cataracts are primarily autosomal dominant disorders, which are also called autosomal dominant congenital cataract, resulting in blindness...
BACKGROUND
Almost one-third of congenital cataracts are primarily autosomal dominant disorders, which are also called autosomal dominant congenital cataract, resulting in blindness and clouding of the lens. The purpose of this study was to identify the disease-causing mutation in a Chinese family affected by bilateral, autosomal dominant congenital cataract.
METHODS
The detection of candidate gene mutation and the linkage analysis of microsatellite markers were performed for the known candidate genes. Molecular mapping and cloning of candidate genes were used in all affected family members to screen for potential genetic mutations and the mutation was confirmed by single enzyme digestion.
RESULTS
The proband was diagnosed with isolated, congenital cataract without the typical clinical manifestations of cataract, which include diabetes, porencephaly, sporadic intracerebral hemorrhage, and glomerulopathy. A novel mutation, c.2345 G > C (Gly782Ala), in exon 31 of the collagen type IV αlpha1 (COL4A1) gene, which encodes the collagen alpha-1(IV) chain, was found to be associated with autosomal dominant congenital cataract in a Chinese family. This mutation was not found in unaffected family members or in 200 unrelated controls. Sequence analysis confirmed that the Gly782 amino acid residue is highly conserved.
CONCLUSIONS
The novel mutation (c.2345 G > C) of the COL4A1 gene is the first report of a non-syndromic, autosomal dominant congenital cataract, thereby highlighting the important role of type IV collagen in the physiological and optical properties of the lens.
Topics: Asian People; Cataract; Chromosomes, Human, Pair 13; Collagen Type IV; Evolution, Molecular; Exons; Female; Genetic Variation; Humans; Linkage Disequilibrium; Male; Microsatellite Repeats; Pedigree; Sequence Analysis
PubMed: 25124159
DOI: 10.1186/s12881-014-0097-2 -
AJNR. American Journal of Neuroradiology 1986Periventricular leukomalacia (PVL) is well recognized as a relatively uncommon yet particularly serious complication of prematurity. Although the sonographic features of...
Periventricular leukomalacia (PVL) is well recognized as a relatively uncommon yet particularly serious complication of prematurity. Although the sonographic features of PVL have been described, its association with intraventricular hemorrhage (IVH) has not been emphasized. Reviewing 26 consecutive cases of PVL in neonates of 34 weeks or less gestational age, significant associated hemorrhage was found in six (23%). Small quantities of blood were also noted in most of the other 20 infants. Of the six infants with both significant IVH and PVL, five required ventricular shunt and all had particularly poor clinical outcomes. In the neonates who required surgical intervention, rapid ventricular enlargement was accompanied by extensive periventricular cyst formation. Eventually, the septations within the cysts and frequently even the ependyma of superior/posterior lateral ventricles degenerated. Cysts merged imperceptibly with the ventricles giving an appearance that mimicked severe hydrocephalus. This was termed "pseudoventricle formation," as the large intracerebral cerebrospinal fluid spaces are primarily porencephaly and not enlarged ventricles. Response to shunting was minimal by sonography in all five cases and multiple shunt revisions were required in four. Clinical follow-up in children with significant IVH in combination with PVL has shown severe mental retardation and tetraplegia in all cases.
Topics: Cerebral Hemorrhage; Encephalomalacia; Humans; Infant, Newborn; Infant, Premature, Diseases; Prognosis; Ultrasonography
PubMed: 3085449
DOI: No ID Found -
Journal of Clinical and Diagnostic... Nov 2014A 2-day-old male child presented with history of enlarged head and seizures since birth, born by caesarean section. Head circumference was 56 cm (dilated) with widely...
A 2-day-old male child presented with history of enlarged head and seizures since birth, born by caesarean section. Head circumference was 56 cm (dilated) with widely open anterior and posterior fontanelle. Routine investigations were within normal limits. CT head revealed a large non-enhancing fluid attenuating cystic lesion in posterior parietal and occipital region with communicating to dilated bilateral lateral ventricles and subarachnoid space.
PubMed: 25584288
DOI: 10.7860/JCDR/2014/9981.5140