Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

Gillian I Rice, Naoki Kitabayashi, Magalie Barth, Tracy A Briggs, Annabel C E Burton, Maria Luisa Carpanelli, Alfredo M Cerisola, Cindy Colson, Russell C Dale, Federica Rachele Danti, Niklas Darin, Begoña De Azua, Valentina De Giorgis, Christian G L De Goede, Isabelle Desguerre, Corinne De Laet, Atieh Eslahi, Michael C Fahey, Penny Fallon, Alex Fay & 32 others Elisa Fazzi, Mark P Gorman, Nirmala Rani Gowrinathan, Marie Hully, Manju A Kurian, Nicolas Leboucq, Jean-Pierre S-M Lin, Matthew A Lines, Soe S Mar, Reza Maroofian, Laura Martí-Sanchez, Gary McCullagh, Majid Mojarrad, Vinodh Narayanan, Simona Orcesi, Juan Dario Ortigoza-Escobar, Belén Pérez-Dueñas, Florence Petit, Keri M Ramsey, Magnhild Rasmussen, François Rivier, Pilar Rodríguez-Pombo, Agathe Roubertie, Tommy I Stödberg, Mehran Beiraghi Toosi, Annick Toutain, Florence Uettwiller, Nicole Ulrick, Adeline Vanderver, Amy Waldman, John H Livingston, Yanick J Crow

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations inADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations inADAR1are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.

Original languageEnglish
Pages (from-to)166-184
Number of pages19
JournalNeuropediatrics
Volume48
Issue number3
DOIs
Publication statusPublished - Jun 2017

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Interferons
Biomarkers
Mutation
Aicardi Syndrome
Spastic Paraparesis
Dystonic Disorders
Phenotype
Corpus Striatum
Interferon Type I
Muscle Spasticity
Missense Mutation
Neuroimaging
Necrosis
Up-Regulation
Psychology
Genes

Keywords

  • Journal Article

Cite this

Rice, G. I., Kitabayashi, N., Barth, M., Briggs, T. A., Burton, A. C. E., Carpanelli, M. L., ... Crow, Y. J. (2017). Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease. Neuropediatrics, 48(3), 166-184. https://doi.org/10.1055/s-0037-1601449

Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease. / Rice, Gillian I; Kitabayashi, Naoki; Barth, Magalie; Briggs, Tracy A; Burton, Annabel C E; Carpanelli, Maria Luisa; Cerisola, Alfredo M; Colson, Cindy; Dale, Russell C; Danti, Federica Rachele; Darin, Niklas; De Azua, Begoña; De Giorgis, Valentina; De Goede, Christian G L; Desguerre, Isabelle; De Laet, Corinne; Eslahi, Atieh; Fahey, Michael C; Fallon, Penny; Fay, Alex; Fazzi, Elisa; Gorman, Mark P; Gowrinathan, Nirmala Rani; Hully, Marie; Kurian, Manju A; Leboucq, Nicolas; Lin, Jean-Pierre S-M; Lines, Matthew A; Mar, Soe S; Maroofian, Reza; Martí-Sanchez, Laura; McCullagh, Gary; Mojarrad, Majid; Narayanan, Vinodh; Orcesi, Simona; Ortigoza-Escobar, Juan Dario; Pérez-Dueñas, Belén; Petit, Florence; Ramsey, Keri M; Rasmussen, Magnhild; Rivier, François; Rodríguez-Pombo, Pilar; Roubertie, Agathe; Stödberg, Tommy I; Toosi, Mehran Beiraghi; Toutain, Annick; Uettwiller, Florence; Ulrick, Nicole; Vanderver, Adeline; Waldman, Amy; Livingston, John H; Crow, Yanick J.

In: Neuropediatrics, Vol. 48, No. 3, 06.2017, p. 166-184.

Research output: Contribution to journalArticle

Rice, GI, Kitabayashi, N, Barth, M, Briggs, TA, Burton, ACE, Carpanelli, ML, Cerisola, AM, Colson, C, Dale, RC, Danti, FR, Darin, N, De Azua, B, De Giorgis, V, De Goede, CGL, Desguerre, I, De Laet, C, Eslahi, A, Fahey, MC, Fallon, P, Fay, A, Fazzi, E, Gorman, MP, Gowrinathan, NR, Hully, M, Kurian, MA, Leboucq, N, Lin, J-PS-M, Lines, MA, Mar, SS, Maroofian, R, Martí-Sanchez, L, McCullagh, G, Mojarrad, M, Narayanan, V, Orcesi, S, Ortigoza-Escobar, JD, Pérez-Dueñas, B, Petit, F, Ramsey, KM, Rasmussen, M, Rivier, F, Rodríguez-Pombo, P, Roubertie, A, Stödberg, TI, Toosi, MB, Toutain, A, Uettwiller, F, Ulrick, N, Vanderver, A, Waldman, A, Livingston, JH & Crow, YJ 2017, 'Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease', Neuropediatrics, vol. 48, no. 3, pp. 166-184. https://doi.org/10.1055/s-0037-1601449
Rice GI, Kitabayashi N, Barth M, Briggs TA, Burton ACE, Carpanelli ML et al. Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease. Neuropediatrics. 2017 Jun;48(3):166-184. https://doi.org/10.1055/s-0037-1601449
Rice, Gillian I ; Kitabayashi, Naoki ; Barth, Magalie ; Briggs, Tracy A ; Burton, Annabel C E ; Carpanelli, Maria Luisa ; Cerisola, Alfredo M ; Colson, Cindy ; Dale, Russell C ; Danti, Federica Rachele ; Darin, Niklas ; De Azua, Begoña ; De Giorgis, Valentina ; De Goede, Christian G L ; Desguerre, Isabelle ; De Laet, Corinne ; Eslahi, Atieh ; Fahey, Michael C ; Fallon, Penny ; Fay, Alex ; Fazzi, Elisa ; Gorman, Mark P ; Gowrinathan, Nirmala Rani ; Hully, Marie ; Kurian, Manju A ; Leboucq, Nicolas ; Lin, Jean-Pierre S-M ; Lines, Matthew A ; Mar, Soe S ; Maroofian, Reza ; Martí-Sanchez, Laura ; McCullagh, Gary ; Mojarrad, Majid ; Narayanan, Vinodh ; Orcesi, Simona ; Ortigoza-Escobar, Juan Dario ; Pérez-Dueñas, Belén ; Petit, Florence ; Ramsey, Keri M ; Rasmussen, Magnhild ; Rivier, François ; Rodríguez-Pombo, Pilar ; Roubertie, Agathe ; Stödberg, Tommy I ; Toosi, Mehran Beiraghi ; Toutain, Annick ; Uettwiller, Florence ; Ulrick, Nicole ; Vanderver, Adeline ; Waldman, Amy ; Livingston, John H ; Crow, Yanick J. / Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease. In: Neuropediatrics. 2017 ; Vol. 48, No. 3. pp. 166-184.
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AU - Kitabayashi, Naoki

AU - Barth, Magalie

AU - Briggs, Tracy A

AU - Burton, Annabel C E

AU - Carpanelli, Maria Luisa

AU - Cerisola, Alfredo M

AU - Colson, Cindy

AU - Dale, Russell C

AU - Danti, Federica Rachele

AU - Darin, Niklas

AU - De Azua, Begoña

AU - De Giorgis, Valentina

AU - De Goede, Christian G L

AU - Desguerre, Isabelle

AU - De Laet, Corinne

AU - Eslahi, Atieh

AU - Fahey, Michael C

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AU - Fay, Alex

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AU - Lines, Matthew A

AU - Mar, Soe S

AU - Maroofian, Reza

AU - Martí-Sanchez, Laura

AU - McCullagh, Gary

AU - Mojarrad, Majid

AU - Narayanan, Vinodh

AU - Orcesi, Simona

AU - Ortigoza-Escobar, Juan Dario

AU - Pérez-Dueñas, Belén

AU - Petit, Florence

AU - Ramsey, Keri M

AU - Rasmussen, Magnhild

AU - Rivier, François

AU - Rodríguez-Pombo, Pilar

AU - Roubertie, Agathe

AU - Stödberg, Tommy I

AU - Toosi, Mehran Beiraghi

AU - Toutain, Annick

AU - Uettwiller, Florence

AU - Ulrick, Nicole

AU - Vanderver, Adeline

AU - Waldman, Amy

AU - Livingston, John H

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DO - 10.1055/s-0037-1601449

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VL - 48

SP - 166

EP - 184

JO - Neuropediatrics

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