PortalPublikationenDisruption of a miR-29 binding site leading to COL4A1 upregu...

Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL

Standard

Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL. / Verdura, Edgard; Hervé, Dominique; Bergametti, Françoise; Jacquet, Clémence; Morvan, Typhaine; Prieto-Morin, Carol; Mackowiak, Alexandre; Manchon, Eric; Hosseini, Hassan; Cordonnier, Charlotte; Girard-Buttaz, Isabelle; Rosenstingl, Sophie; Hagel, Christian; Kuhlenbaümer, Gregor; Leca-Radu, Elena; Goux, Didier; Fleming, Lauren; Van Agtmael, Tom; Chabriat, Hugues; Chapon, Françoise; Tournier-Lasserve, Elisabeth.

in: ANN NEUROL, Jahrgang 80, Nr. 5, 11.2016, S. 741-753.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Verdura, E, Hervé, D, Bergametti, F, Jacquet, C, Morvan, T, Prieto-Morin, C, Mackowiak, A, Manchon, E, Hosseini, H, Cordonnier, C, Girard-Buttaz, I, Rosenstingl, S, Hagel, C, Kuhlenbaümer, G, Leca-Radu, E, Goux, D, Fleming, L, Van Agtmael, T, Chabriat, H, Chapon, F & Tournier-Lasserve, E 2016, 'Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL', ANN NEUROL, Jg. 80, Nr. 5, S. 741-753. https://doi.org/10.1002/ana.24782

APA

Verdura, E., Hervé, D., Bergametti, F., Jacquet, C., Morvan, T., Prieto-Morin, C., Mackowiak, A., Manchon, E., Hosseini, H., Cordonnier, C., Girard-Buttaz, I., Rosenstingl, S., Hagel, C., Kuhlenbaümer, G., Leca-Radu, E., Goux, D., Fleming, L., Van Agtmael, T., Chabriat, H., ... Tournier-Lasserve, E. (2016). Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL. ANN NEUROL, 80(5), 741-753. https://doi.org/10.1002/ana.24782

Vancouver

Verdura E, Hervé D, Bergametti F, Jacquet C, Morvan T, Prieto-Morin C et al. Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL. ANN NEUROL. 2016 Nov;80(5):741-753. https://doi.org/10.1002/ana.24782

Bibtex

@article{d2edbf33204042418bca99d970e63130,
title = "Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL",
abstract = "OBJECTIVE: Cerebral small vessel disease (cSVD) is an heterogeneous group of disorders. Screening of known cSVD genes identifies the causative mutation in less than 15% of familial cSVD cases. We sought to identify novel causes of cSVD.METHODS: We used linkage analysis and exome sequencing to identify the causal mutation in a French cSVD family. The identified candidate gene was then screened in 202 cSVD unrelated probands, including one proband from the first reported Pontine Autosomal Dominant MicroAngiopathy with Leukoencephalopathy (PADMAL) family. Sanger sequencing was used to confirm variants in all mutated probands and analyze their segregation in probands' relatives. Mutation consequences were assessed with luciferase reporter assays and RT-qPCR.RESULTS: A candidate heterozygous variant located in a predicted miR-29 microRNA binding site, within the 3'UTR region of COL4A1, was identified in the large French cSVD family. Five additional unrelated probands, including the PADMAL proband, harbored heterozygous variants in this microRNA binding site. Variants cosegregated with the affected phenotype and cumulative LOD score reached 6.03, establishing linkage to this locus. A highly significant difference was observed when comparing the number of variants within this binding site in cases and controls (p=1.77 x 10E-12). RT-qPCR analyses of patients' primary fibroblasts and luciferase reporter assays strongly favor an upregulation of COL4A1 mediated by disruption of miR-29 binding to its target site. MRI features were characterized by the presence of multiple pontine infarcts in all symptomatic mutation carriers.INTERPRETATION: Mutations upregulating COL4A1 expression lead to PADMAL, a severe early-onset ischaemic cSVD, distinct from the various phenotypes associated with COL4A1 missense glycine mutations. This article is protected by copyright. All rights reserved.",
author = "Edgard Verdura and Dominique Herv{\'e} and Fran{\c c}oise Bergametti and Cl{\'e}mence Jacquet and Typhaine Morvan and Carol Prieto-Morin and Alexandre Mackowiak and Eric Manchon and Hassan Hosseini and Charlotte Cordonnier and Isabelle Girard-Buttaz and Sophie Rosenstingl and Christian Hagel and Gregor Kuhlenba{\"u}mer and Elena Leca-Radu and Didier Goux and Lauren Fleming and {Van Agtmael}, Tom and Hugues Chabriat and Fran{\c c}oise Chapon and Elisabeth Tournier-Lasserve",
note = "{\textcopyright} 2016 American Neurological Association.",
year = "2016",
month = nov,
doi = "10.1002/ana.24782",
language = "English",
volume = "80",
pages = "741--753",
journal = "ANN NEUROL",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Disruption of a miR-29 binding site leading to COL4A1 upregulation causes PADMAL

AU - Verdura, Edgard

AU - Hervé, Dominique

AU - Bergametti, Françoise

AU - Jacquet, Clémence

AU - Morvan, Typhaine

AU - Prieto-Morin, Carol

AU - Mackowiak, Alexandre

AU - Manchon, Eric

AU - Hosseini, Hassan

AU - Cordonnier, Charlotte

AU - Girard-Buttaz, Isabelle

AU - Rosenstingl, Sophie

AU - Hagel, Christian

AU - Kuhlenbaümer, Gregor

AU - Leca-Radu, Elena

AU - Goux, Didier

AU - Fleming, Lauren

AU - Van Agtmael, Tom

AU - Chabriat, Hugues

AU - Chapon, Françoise

AU - Tournier-Lasserve, Elisabeth

N1 - © 2016 American Neurological Association.

PY - 2016/11

Y1 - 2016/11

N2 - OBJECTIVE: Cerebral small vessel disease (cSVD) is an heterogeneous group of disorders. Screening of known cSVD genes identifies the causative mutation in less than 15% of familial cSVD cases. We sought to identify novel causes of cSVD.METHODS: We used linkage analysis and exome sequencing to identify the causal mutation in a French cSVD family. The identified candidate gene was then screened in 202 cSVD unrelated probands, including one proband from the first reported Pontine Autosomal Dominant MicroAngiopathy with Leukoencephalopathy (PADMAL) family. Sanger sequencing was used to confirm variants in all mutated probands and analyze their segregation in probands' relatives. Mutation consequences were assessed with luciferase reporter assays and RT-qPCR.RESULTS: A candidate heterozygous variant located in a predicted miR-29 microRNA binding site, within the 3'UTR region of COL4A1, was identified in the large French cSVD family. Five additional unrelated probands, including the PADMAL proband, harbored heterozygous variants in this microRNA binding site. Variants cosegregated with the affected phenotype and cumulative LOD score reached 6.03, establishing linkage to this locus. A highly significant difference was observed when comparing the number of variants within this binding site in cases and controls (p=1.77 x 10E-12). RT-qPCR analyses of patients' primary fibroblasts and luciferase reporter assays strongly favor an upregulation of COL4A1 mediated by disruption of miR-29 binding to its target site. MRI features were characterized by the presence of multiple pontine infarcts in all symptomatic mutation carriers.INTERPRETATION: Mutations upregulating COL4A1 expression lead to PADMAL, a severe early-onset ischaemic cSVD, distinct from the various phenotypes associated with COL4A1 missense glycine mutations. This article is protected by copyright. All rights reserved.

AB - OBJECTIVE: Cerebral small vessel disease (cSVD) is an heterogeneous group of disorders. Screening of known cSVD genes identifies the causative mutation in less than 15% of familial cSVD cases. We sought to identify novel causes of cSVD.METHODS: We used linkage analysis and exome sequencing to identify the causal mutation in a French cSVD family. The identified candidate gene was then screened in 202 cSVD unrelated probands, including one proband from the first reported Pontine Autosomal Dominant MicroAngiopathy with Leukoencephalopathy (PADMAL) family. Sanger sequencing was used to confirm variants in all mutated probands and analyze their segregation in probands' relatives. Mutation consequences were assessed with luciferase reporter assays and RT-qPCR.RESULTS: A candidate heterozygous variant located in a predicted miR-29 microRNA binding site, within the 3'UTR region of COL4A1, was identified in the large French cSVD family. Five additional unrelated probands, including the PADMAL proband, harbored heterozygous variants in this microRNA binding site. Variants cosegregated with the affected phenotype and cumulative LOD score reached 6.03, establishing linkage to this locus. A highly significant difference was observed when comparing the number of variants within this binding site in cases and controls (p=1.77 x 10E-12). RT-qPCR analyses of patients' primary fibroblasts and luciferase reporter assays strongly favor an upregulation of COL4A1 mediated by disruption of miR-29 binding to its target site. MRI features were characterized by the presence of multiple pontine infarcts in all symptomatic mutation carriers.INTERPRETATION: Mutations upregulating COL4A1 expression lead to PADMAL, a severe early-onset ischaemic cSVD, distinct from the various phenotypes associated with COL4A1 missense glycine mutations. This article is protected by copyright. All rights reserved.

U2 - 10.1002/ana.24782

DO - 10.1002/ana.24782

M3 - SCORING: Journal article

C2 - 27666438

VL - 80

SP - 741

EP - 753

JO - ANN NEUROL

JF - ANN NEUROL

SN - 0364-5134

IS - 5

ER -