PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum

Katrine M. Johannesen; Elena Gardella; Cathrine E. Gjerulfsen; Allan Bayat; Rob P.W. Rouhl; Margot Reijnders; Sandra Whalen; Boris Keren; Julien Buratti; Thomas Courtin; Klaas J. Wierenga; Bertrand Isidor; Amélie Piton; Laurence Faivre; Aurore Garde; Sébastien Moutton; Frédéric Tran-Mau-Them; Anne Sophie Denommé-Pichon; Christine Coubes; Austin Larson; Michael J. Esser; Juan Pablo Appendino; Walla Al-Hertani; Beatriz Gamboni; Alejandra Mampel; Lía Mayorga; Alessandro Orsini; Alice Bonuccelli; Agnese Suppiej; Julien Van-Gils; Julie Vogt; Simona Damioli; Lucio Giordano; Stephanie Moortgat; Elaine Wirrell; Sarah Hicks; Usha Kini; Nathan Noble; Helen Stewart; Shailesh Asakar; Julie S. Cohen; Sakku Bai R. Naidu; Ashley Collier; Eva H. Brilstra; Mindy H. Li; Casey Brew; Stefania Bigoni; Davide Ognibene; Rikke S. Møller; Guido Rubboli; PURA study group

doi:10.1212/NXG.0000000000000613

PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum

Katrine M. Johannesen^*, Elena Gardella, Cathrine E. Gjerulfsen, Allan Bayat, Rob P.W. Rouhl, Margot Reijnders, Sandra Whalen, Boris Keren, Julien Buratti, Thomas Courtin, Klaas J. Wierenga, Bertrand Isidor, Amélie Piton, Laurence Faivre, Aurore Garde, Sébastien Moutton, Frédéric Tran-Mau-Them, Anne Sophie Denommé-Pichon, Christine Coubes, Austin LarsonMichael J. Esser, Juan Pablo Appendino, Walla Al-Hertani, Beatriz Gamboni, Alejandra Mampel, Lía Mayorga, Alessandro Orsini, Alice Bonuccelli, Agnese Suppiej, Julien Van-Gils, Julie Vogt, Simona Damioli, Lucio Giordano, Stephanie Moortgat, Elaine Wirrell, Sarah Hicks, Usha Kini, Nathan Noble, Helen Stewart, Shailesh Asakar, Julie S. Cohen, Sakku Bai R. Naidu, Ashley Collier, Eva H. Brilstra, Mindy H. Li, Casey Brew, Stefania Bigoni, Davide Ognibene, Rikke S. Møller, Guido Rubboli, PURA study group

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Abstrakt

Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.

Originalsprog	Engelsk
Artikelnummer	e613
Tidsskrift	Neurology: Genetics
Vol/bind	7
Udgave nummer	6
Antal sider	15
ISSN	2376-7839
DOI	https://doi.org/10.1212/NXG.0000000000000613
Status	Udgivet - 15. dec. 2021

Bibliografisk note

Funding Information:
The authors are deeply grateful for the collaboration and support from all the PURA families, and the authors wish to acknowledge the PURA foundation for their tireless work and commitment to advance the knowledge on PURA syndrome. The authors thank Diana Baralle for inclusion of patients and Dierk Niessing and Robert Janowski for their invaluable support and comments on the manuscript. The authors thank the following for their contributions to the study: Deborah Mitchell-Langlois. The authors thank Jean-François Deleuze, Anne Boland-Augé, and Robert Olaso for the collaboration CEA/JACOB/CNRGH—CHU de Dijon—Inserm.

Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Dokumenter og links

10.1212/NXG.0000000000000613Licens: CC BY-NC-ND

Open Access VersionForlagets udgivne version, 1,06 MBLicens: CC BY-NC-ND

Citationsformater

Johannesen, K. M., Gardella, E., Gjerulfsen, C. E., Bayat, A., Rouhl, R. P. W., Reijnders, M., Whalen, S., Keren, B., Buratti, J., Courtin, T., Wierenga, K. J., Isidor, B., Piton, A., Faivre, L., Garde, A., Moutton, S., Tran-Mau-Them, F., Denommé-Pichon, A. S., Coubes, C., ... PURA study group (2021). PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum. Neurology: Genetics, 7(6), [e613]. https://doi.org/10.1212/NXG.0000000000000613

Johannesen, Katrine M. ; Gardella, Elena ; Gjerulfsen, Cathrine E. ; Bayat, Allan ; Rouhl, Rob P.W. ; Reijnders, Margot ; Whalen, Sandra ; Keren, Boris ; Buratti, Julien ; Courtin, Thomas ; Wierenga, Klaas J. ; Isidor, Bertrand ; Piton, Amélie ; Faivre, Laurence ; Garde, Aurore ; Moutton, Sébastien ; Tran-Mau-Them, Frédéric ; Denommé-Pichon, Anne Sophie ; Coubes, Christine ; Larson, Austin ; Esser, Michael J. ; Appendino, Juan Pablo ; Al-Hertani, Walla ; Gamboni, Beatriz ; Mampel, Alejandra ; Mayorga, Lía ; Orsini, Alessandro ; Bonuccelli, Alice ; Suppiej, Agnese ; Van-Gils, Julien ; Vogt, Julie ; Damioli, Simona ; Giordano, Lucio ; Moortgat, Stephanie ; Wirrell, Elaine ; Hicks, Sarah ; Kini, Usha ; Noble, Nathan ; Stewart, Helen ; Asakar, Shailesh ; Cohen, Julie S. ; Naidu, Sakku Bai R. ; Collier, Ashley ; Brilstra, Eva H. ; Li, Mindy H. ; Brew, Casey ; Bigoni, Stefania ; Ognibene, Davide ; Møller, Rikke S. ; Rubboli, Guido ; PURA study group. / PURA-Related Developmental and Epileptic Encephalopathy : Phenotypic and Genotypic Spectrum. I: Neurology: Genetics. 2021 ; Bind 7, Nr. 6.

@article{629ed5cda03f4693817e61374a09bb6d,

title = "PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum",

abstract = "Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.",

author = "Johannesen, {Katrine M.} and Elena Gardella and Gjerulfsen, {Cathrine E.} and Allan Bayat and Rouhl, {Rob P.W.} and Margot Reijnders and Sandra Whalen and Boris Keren and Julien Buratti and Thomas Courtin and Wierenga, {Klaas J.} and Bertrand Isidor and Am{\'e}lie Piton and Laurence Faivre and Aurore Garde and S{\'e}bastien Moutton and Fr{\'e}d{\'e}ric Tran-Mau-Them and Denomm{\'e}-Pichon, {Anne Sophie} and Christine Coubes and Austin Larson and Esser, {Michael J.} and Appendino, {Juan Pablo} and Walla Al-Hertani and Beatriz Gamboni and Alejandra Mampel and L{\'i}a Mayorga and Alessandro Orsini and Alice Bonuccelli and Agnese Suppiej and Julien Van-Gils and Julie Vogt and Simona Damioli and Lucio Giordano and Stephanie Moortgat and Elaine Wirrell and Sarah Hicks and Usha Kini and Nathan Noble and Helen Stewart and Shailesh Asakar and Cohen, {Julie S.} and Naidu, {Sakku Bai R.} and Ashley Collier and Brilstra, {Eva H.} and Li, {Mindy H.} and Casey Brew and Stefania Bigoni and Davide Ognibene and M{\o}ller, {Rikke S.} and Guido Rubboli and {PURA study group}",

note = "Funding Information: The authors are deeply grateful for the collaboration and support from all the PURA families, and the authors wish to acknowledge the PURA foundation for their tireless work and commitment to advance the knowledge on PURA syndrome. The authors thank Diana Baralle for inclusion of patients and Dierk Niessing and Robert Janowski for their invaluable support and comments on the manuscript. The authors thank the following for their contributions to the study: Deborah Mitchell-Langlois. The authors thank Jean-Fran{\c c}ois Deleuze, Anne Boland-Aug{\'e}, and Robert Olaso for the collaboration CEA/JACOB/CNRGH—CHU de Dijon—Inserm. Publisher Copyright: Copyright {\textcopyright} 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",

year = "2021",

month = dec,

day = "15",

doi = "10.1212/NXG.0000000000000613",

language = "English",

volume = "7",

journal = "Neurology: Genetics",

issn = "2376-7839",

publisher = "Wolters Kluwer Health",

number = "6",

}

Johannesen, KM , Gardella, E, Gjerulfsen, CE, Bayat, A, Rouhl, RPW, Reijnders, M, Whalen, S, Keren, B, Buratti, J, Courtin, T, Wierenga, KJ, Isidor, B, Piton, A, Faivre, L, Garde, A, Moutton, S, Tran-Mau-Them, F, Denommé-Pichon, AS, Coubes, C, Larson, A, Esser, MJ, Appendino, JP, Al-Hertani, W, Gamboni, B, Mampel, A, Mayorga, L, Orsini, A, Bonuccelli, A, Suppiej, A, Van-Gils, J, Vogt, J, Damioli, S, Giordano, L, Moortgat, S, Wirrell, E, Hicks, S, Kini, U, Noble, N, Stewart, H, Asakar, S, Cohen, JS, Naidu, SBR, Collier, A, Brilstra, EH, Li, MH, Brew, C, Bigoni, S, Ognibene, D, Møller, RS, Rubboli, G & PURA study group 2021, 'PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum', Neurology: Genetics, bind 7, nr. 6, e613. https://doi.org/10.1212/NXG.0000000000000613

PURA-Related Developmental and Epileptic Encephalopathy : Phenotypic and Genotypic Spectrum. / Johannesen, Katrine M.; Gardella, Elena; Gjerulfsen, Cathrine E.; Bayat, Allan; Rouhl, Rob P.W.; Reijnders, Margot; Whalen, Sandra; Keren, Boris; Buratti, Julien; Courtin, Thomas; Wierenga, Klaas J.; Isidor, Bertrand; Piton, Amélie; Faivre, Laurence; Garde, Aurore; Moutton, Sébastien; Tran-Mau-Them, Frédéric; Denommé-Pichon, Anne Sophie; Coubes, Christine; Larson, Austin; Esser, Michael J.; Appendino, Juan Pablo; Al-Hertani, Walla; Gamboni, Beatriz; Mampel, Alejandra; Mayorga, Lía; Orsini, Alessandro; Bonuccelli, Alice; Suppiej, Agnese; Van-Gils, Julien; Vogt, Julie; Damioli, Simona; Giordano, Lucio; Moortgat, Stephanie; Wirrell, Elaine; Hicks, Sarah; Kini, Usha; Noble, Nathan; Stewart, Helen; Asakar, Shailesh; Cohen, Julie S.; Naidu, Sakku Bai R.; Collier, Ashley; Brilstra, Eva H.; Li, Mindy H.; Brew, Casey; Bigoni, Stefania; Ognibene, Davide; Møller, Rikke S.; Rubboli, Guido; PURA study group.

I: Neurology: Genetics, Bind 7, Nr. 6, e613, 15.12.2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - PURA-Related Developmental and Epileptic Encephalopathy

T2 - Phenotypic and Genotypic Spectrum

AU - Johannesen, Katrine M.

AU - Gardella, Elena

AU - Gjerulfsen, Cathrine E.

AU - Bayat, Allan

AU - Rouhl, Rob P.W.

AU - Reijnders, Margot

AU - Whalen, Sandra

AU - Keren, Boris

AU - Buratti, Julien

AU - Courtin, Thomas

AU - Wierenga, Klaas J.

AU - Isidor, Bertrand

AU - Piton, Amélie

AU - Faivre, Laurence

AU - Garde, Aurore

AU - Moutton, Sébastien

AU - Tran-Mau-Them, Frédéric

AU - Denommé-Pichon, Anne Sophie

AU - Coubes, Christine

AU - Larson, Austin

AU - Esser, Michael J.

AU - Appendino, Juan Pablo

AU - Al-Hertani, Walla

AU - Gamboni, Beatriz

AU - Mampel, Alejandra

AU - Mayorga, Lía

AU - Orsini, Alessandro

AU - Bonuccelli, Alice

AU - Suppiej, Agnese

AU - Van-Gils, Julien

AU - Vogt, Julie

AU - Damioli, Simona

AU - Giordano, Lucio

AU - Moortgat, Stephanie

AU - Wirrell, Elaine

AU - Hicks, Sarah

AU - Kini, Usha

AU - Noble, Nathan

AU - Stewart, Helen

AU - Asakar, Shailesh

AU - Cohen, Julie S.

AU - Naidu, Sakku Bai R.

AU - Collier, Ashley

AU - Brilstra, Eva H.

AU - Li, Mindy H.

AU - Brew, Casey

AU - Bigoni, Stefania

AU - Ognibene, Davide

AU - Møller, Rikke S.

AU - Rubboli, Guido

AU - PURA study group

N1 - Funding Information: The authors are deeply grateful for the collaboration and support from all the PURA families, and the authors wish to acknowledge the PURA foundation for their tireless work and commitment to advance the knowledge on PURA syndrome. The authors thank Diana Baralle for inclusion of patients and Dierk Niessing and Robert Janowski for their invaluable support and comments on the manuscript. The authors thank the following for their contributions to the study: Deborah Mitchell-Langlois. The authors thank Jean-François Deleuze, Anne Boland-Augé, and Robert Olaso for the collaboration CEA/JACOB/CNRGH—CHU de Dijon—Inserm. Publisher Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2021/12/15

Y1 - 2021/12/15

N2 - Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.

AB - Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.

U2 - 10.1212/NXG.0000000000000613

DO - 10.1212/NXG.0000000000000613

M3 - Journal article

C2 - 34790866

AN - SCOPUS:85121913018

VL - 7

JO - Neurology: Genetics

JF - Neurology: Genetics

SN - 2376-7839

IS - 6

M1 - e613

ER -

PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum

Abstrakt

Bibliografisk note

Dokumenter og links

Fingeraftryk

Citationsformater