Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterotrimers composed of collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) constitute one of the most abundant components of nearly all basement membranes. Accordingly, mutations in COL4A1 or COL4A2 are pleiotropic and contribute to a broad spectrum of disorders, including myopathy, glaucoma and hemorrhagic stroke. Here, we summarize the contributions of COL4A1 and COL4A2 mutations in human disease, integrate knowledge gained from model organisms and evaluate the implications for pathogenic mechanisms and therapeutic approaches.
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PMID:COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. 2291 37

Background and Purpose- Pontine autosomal dominant microangiopathy and leukoencephalopathy, a recently defined subtype of cerebral small vessel disease, is associated with mutations in COL4A1 (collagen type IV alpha 1 chain) 3' untranslated region. We here describe a pontine autosomal dominant microangiopathy and leukoencephalopathy pedigree with COL4A1 mutation presenting both pontine and cervical spinal cord involvement. Methods- For the diagnostic purpose, brain and spinal magnetic resonance imaging scanning, skin biopsy, and whole-exome sequencing were performed on the patients in the pedigree. Suspected pathogenic variants were further confirmed by cosegregation analysis using Sanger sequencing in the family members. Results- We identified a mutation located at the binding site of miR-29 (microRNA-29) in 3' untranslated region of COL4A1(c.*32G>A). The pontine autosomal dominant microangiopathy and leukoencephalopathy patients in this pedigree carried this variant, whereas other healthy family members but one did not. Magnetic resonance imaging showed lesions in the pons, white matter, and cervical spinal cord. Skin biopsy revealed thickened basal lamina in vessels. Conclusions- For the first time, we reported cervical spinal involvement in pontine autosomal dominant microangiopathy and leukoencephalopathy and expanded the clinical spectrum of this disease.
Stroke 2019 09
PMID:Cervical Spinal Involvement in a Chinese Pedigree With Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy Caused by a 3' Untranslated Region Mutation of COL4A1 Gene. 3136 14

Stroke is a major cause of mortality and morbidity with a wide variety of etiological risk factors. Cerebral small vessel disease (SVD) is an important cause of stroke in the young with several hereditary disorders affecting these small blood vessels. Mutations in the COL4A1 gene (COL4A1) have been shown to be associated with a broad range of disorders including hemorrhagic stroke, myopathy, glaucoma and others. We report a rare case of stroke in an intellectually disabled 18-year-old girl with radiological evidence of basal ganglia microbleeds, periventricular white matter signal changes and porencephalic cyst. Ophthalmic examination revealed bilateral microcornea and Axenfeld-Rieger anomaly. At autopsy there were hemorrhagic lesions at multiple sites within the brain. Histology revealed thickened small-caliber vessels which demonstrated disruption and fragmentation of the basement membrane by collagen type IV alpha 1 immunohistochemistry and by electron microscopy. A missense COL4A1 mutation involving glycine residue was detected in the patient. The present case illustrates the clinicopathological spectrum of COL4A1-related cerebral SVD presenting as hemorrhagic stroke in the young with porencephaly, intellectual disability, and Axenfield-Rieger anomaly and thus adds to the clinical heterogeneity of this genetic disorder.
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PMID:Cerebral small vessel disease with hemorrhagic stroke related to COL4A1 mutation: A case report. 3180 7