Main features of COL4A1-COL4A2 related cerebral microangiopathies

Guey, Stéphanie; Hervé, Dominique

doi:10.1016/j.cccb.2022.100140

Cited by 11 publications

(12 citation statements)

References 40 publications

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“…However, missense mutations involving non-glycine residues of the triple-helix were also reported ( 4 ). The substitution of highly conserved residues in the triple-helical domain is assumed to change the whole heterotrimer structure, which may affect the secretion of heterotrimers in the matrix and finally lead to structural or functional abnormalities of basement membranes ( 5 ). In this case, the young male patient had recurrent ischemic stroke and leukoencephalopathy, and the pons were significantly affected, which was quite different from CADASIL.…”

Section: Discussionmentioning

confidence: 99%

“…Most COL4A1 mutations are autosomal dominant inheritance, but the phenotypic spectrum is highly heterogeneous. Moreover, penetration of COL4A1 mutations is rather incomplete, suggesting that modifying factors may be involved ( 5 ). In this case report, the mutation in the COL4A1 of the patient was inherited from his mother, who was asymptomatic and had no history of cerebrovascular disease.…”

Section: Discussionmentioning

confidence: 99%

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Case report: Recurrent pontine stroke and leukoencephalopathy in a patient with de novo mutation in COL4A1

Zhang,

Fan,

Zhang

et al. 2023

Front. Neurol.

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This report presents a case of pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL) in a 35 year-old male patient. The patient exhibited a consistent history of recurrent ischemic strokes, concentrated primarily in the pons region, accompanied by concurrent manifestations of leukoencephalopathy and microbleeds. Genetic evaluation revealed a heterozygous missense mutation consistent with c.3431C>G, p. Thr1144Arg substitution within exon 40 of the COL4A1 gene. This mutation was also identified in the patient’s mother, affirming an autosomal dominant inheritance model. Our findings serve as testament to the potential role of mutation in the exon 40 of COL4A1 in the pathogenesis and progression of PADMAL, contributing to ongoing efforts aimed at better understanding the genetic basis of this debilitating disorder.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Case report: Recurrent pontine stroke and leukoencephalopathy in a patient with de novo mutation in COL4A1

Zhang,

Fan,

Zhang

et al. 2023

Front. Neurol.

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“…Genetic causes of stroke in the young are becoming better understood with improved availability of genetic testing. Such causes include genetic vasculopathies such as COL4A1 disorders, which presents with phenotypes varying from porencephaly, recurrent ischemic or hemorrhagic strokes, or isolated migraine with aura [83]. Other collagen disorders, including COL3A1 and Marfan syndrome, increase the risk of cervical arterial dissection as a cause of stroke [84].…”

Section: Genetic Causesmentioning

confidence: 99%

Stroke in the young

Fraser

Pabst

Smith

2023

Current Opinion in Neurology

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Purpose of reviewThe purpose of this review is to review recent findings regarding stroke epidemiology, etiologies, and treatment in children and young adults.Recent findingsIncidence in young adults is increasing, and incidence, recurrence, and survival is worse in patients with cryptogenic stroke and in developing countries. Careful consideration of patent foramen ovale closure is now recommended in young adults with cryptogenic stroke. Thrombectomy has recently been extended to carefully selected children with acute ischemic stroke, and two recent publications strongly suggest that it can be beneficial for children. Sickle cell is also an important global contributor to stroke burden, but hydroxyurea can be a cost effective medication for stroke prevention in children. Recent advances in genetic testing and treatments may improve outcomes for patients with monogenic causes of stroke, such as deficiency of adenosine deaminase 2, hemophilia, and Fabry's disease.SummaryStroke in children and young adults is a morbid disease responsible for enormous indirect societal costs and a high burden of years with disability per affected patient. Recent advances have improved access to care for children with large vessel occlusion and adults with rare causes of stroke. Future research may bring effective treatments for other monogenic causes of stroke as well as increasing access to hyperacute therapies for young stroke patients.

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“…Only 11 families have been published and it is not possible to estimate the incidence or prevalence of the disease [ 5 – 9 ]. PADMAL belongs to the group of autosomal dominant cerebrovascular diseases caused by type IV collagen variants [ 10 , 11 ]. Type IV collagens are the main constituent of basement membranes and form mesh-like structures with multiple functions including mechanic strength [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Missense variants affecting these glycine residues may lead to a failure to form proper triple helices [ 12 ]. Protein truncating variants and duplications may also cause cerebrovascular disease, presumably by reduced expression or overexpression of type IV collagens [ 11 , 13 – 15 ]. Clinically, COL4A1/A2 mutations cause a wide variety of phenotypes ranging from fetal death, porencephaly, and intracerebral hemorrhages to cerebral microangiopathy, cervical artery dissection, and some individuals even remain asymptomatic [ 10 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Pontine autosomal dominant microangiopathy with leukoencephalopathy: Col4A1 gene variants in the original family and sporadic stroke

et al. 2023

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Background (1) Description of clinical and cranial MRI features in the original Pontine Autosomal Dominant Microangiopathy with Leukoencephalopathy (PADMAL) family and correlation with the segregation analysis of the causative collagen 4A1 gene (COL4A1) variant. (2) Sequence analysis of the COL4A1 miRNA-binding site containing the causative variant in two independent cross-sectional samples of sporadic stroke patients. Patients and methods Sanger sequencing of the COL4A1 miRNA-binding site in the PADMAL family and 874 sporadic stroke patients. Results PADMAL shows adult-onset usually between 30 and 50 years of age with initial brainstem-related symptoms most commonly dysarthria, with progression to dementia and tetraparesis. Radiologically pontine lacunes are followed by supratentorial white matter involvement. Radiological onset may precede clinical symptoms. We found no variants in the COL4A1 miRNA-binding site of sporadic stroke patients. Conclusion Our results allow an early diagnosis of PADMAL based on cranial MRI, clinical signs, and confirmatory sequencing of the COL4A1 miRNA-29-binding site. COL4A1 miRNA-29-binding site variants do not contribute to a sizeable proportion of sporadic stroke.

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Main features of COL4A1-COL4A2 related cerebral microangiopathies

Cited by 11 publications

References 40 publications

Case report: Recurrent pontine stroke and leukoencephalopathy in a patient with de novo mutation in COL4A1

Case report: Recurrent pontine stroke and leukoencephalopathy in a patient with de novo mutation in COL4A1

Stroke in the young

Pontine autosomal dominant microangiopathy with leukoencephalopathy: Col4A1 gene variants in the original family and sporadic stroke

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