Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.
Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.
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DOI：
10.1055/s-0037-1601449
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发表时间：
2017-06
期刊：
影响因子：
1.4
通讯作者：
Crow YJ
中科院分区：
文献类型：
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作者：
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 JS;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
我们研究了来自37个家族的46例因ADAR1基因突变而患有神经系统疾病的患者的遗传、表型和干扰素状况。临床放射学表型包括aicardii - goutires综合征，孤立的双侧纹状体坏死，神经影像学正常的痉挛性截瘫，进行性痉挛性张力障碍运动障碍和成人发病的颅内钙化心理困难。在5个家族中记录到纯合子错义突变。在23个具有复合杂合突变的家族中，有22个家族的p.Pro193Ala变异处于杂合状态。我们还确定了来自9个家族的11例p.Gly1007Arg显性阴性突变，其中4例患者从头发生，并在3个家族中遗传，与显着的表型变异相关。在34例患者的52份样本中，我们发现外周血中I型干扰素刺激基因转录物显著上调，与对照组（中位数：0.93,IQR: 0.57-1.30）相比，干扰素评分中位数为16.99（四分位数范围[IQR]: 10.64-25.71）。因此，ADAR1的突变与从婴儿期早期到成年期出现的各种临床不同的神经表型相关，这些表型要么是常染色体隐性遗传，要么是显性遗传。在这种情况下，血液中干扰素特征的检测是一种有用的生物标志物。
We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. 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 in ADAR1 are 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.
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影响因子：
11.4
作者：
Heale, Bret S. E.;Keegan, Liam P.;McGurk, Leeanne;Michlewski, Gracjan;Brindle, James;Stanton, Chloe M.;Caceres, Javier F.;O'Connell, Mary A.
通讯作者：
O'Connell, Mary A.
影响因子：
16.8
作者：
通讯作者：
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一个 ADAR1 基因突变家族中的肌张力障碍、智力退化和对称性遗传色素沉着症
影响因子：
8.6
作者：
Tojo, Kana;Sekijima, Yoshiki;Ikeda, Shu-ichi
通讯作者：
Ikeda, Shu-ichi
影响因子：
2
作者：
Crow, Yanick J.;Chase, Diana S.;Schmidt, Johanna Lowenstein;Szynkiewicz, Marcin;Forte, Gabriella M. A.;Gornall, Hannah L.;Oojageer, Anthony;Anderson, Beverley;Pizzino, Amy;Helman, Guy;Abdel-Hamid, Mohamed S.;Abdel-Salam, Ghada M.;Ackroyd, Sam;Aeby, Alec;Agosta, Guillermo;Albin, Catherine;Allon-Shalev, Stavit;Arellano, Montse;Ariaudo, Giada;Aswani, Vijay;Babul-Hirji, Riyana;Baildam, Eileen M.;Bahi-Buisson, Nadia;Bailey, Kathryn M.;Barnerias, Christine;Barth, Magalie;Battini, Roberta;Beresford, Michael W.;Bernard, Genevieve;Bianchi, Marika;de Villemeur, Thierry Billette;Blair, Edward M.;Bloom, Miriam;Burlina, Alberto B.;Carpanelli, Maria Luisa;Carvalho, Daniel R.;Castro-Gago, Manuel;Cavallini, Anna;Cereda, Cristina;Chandler, Kate E.;Chitayat, David A.;Collins, Abigail E.;Sierra Corcoles, Concepcion;Cordeiro, Nuno J. V.;Crichiutti, Giovanni;Dabydeen, Lyvia;Dale, Russell C.;D'Arrigo, Stefano;De Goede, Christian G. E. L.;De Laet, Corinne;De Waele, Liesbeth M. H.;Denzler, Ines;Desguerre, Isabelle;Devriendt, Koenraad;Di Rocco, Maja;Fahey, Michael C.;Fazzi, Elisa;Ferrie, Colin D.;Figueiredo, Antonio;Gener, Blanca;Goizet, Cyril;Gowrinathan, Nirmala R.;Gowrishankar, Kalpana;Hanrahan, Donncha;Isidor, Bertrand;Kara, Lent;Khan, Nasaim;King, Mary D.;Kirk, Edwin P.;Kumar, Ram;Lagae, Lieven;Landrieu, Pierre;Lauffer, Heinz;Laugel, Vincent;La Piana, Roberta;Lim, Ming J.;Lin, Jean-Pierre S. -M.;Linnankivi, Tarja;Mackay, Mark T.;Marom, Daphna R.;Lourenco, Charles Marques;McKee, Shane A.;Moroni, Isabella;Morton, Jenny E. V.;Moutard, Marie-Laure;Murray, Kevin;Nabbout, Rima;Nampoothiri, Sheela;Nunez-Enamorado, Noemi;Oades, Patrick J.;Olivieri, Ivana;Ostergaard, John R.;Perez-Duenas, Belen;Prendiville, Julie S.;Ramesh, Venkateswaran;Rasmussen, Magnhild;Regal, Luc;Ricci, Federica;Rio, Marlene;Rodriguez, Diana;Roubertie, Agathe;Salvatici, Elisabetta;Segers, Karin A.;Sinha, Gyanranjan P.;Soler, Doriette;Spiegel, Ronen;Stoedberg, Tommy I.;Straussberg, Rachel;Swoboda, Kathryn J.;Suri, Mohnish;Tacke, Uta;Tan, Tiong Y.;Naude, Johann te Water;Teik, Keng Wee;Thomas, Maya Mary;Till, Marianne;Tonduti, Davide;Valente, Enza Maria;Van Coster, Rudy Noel;van der Knaap, Marjo S.;Vassallo, Grace;Vijzelaar, Raymon;Vogt, Julie;Wallace, Geoffrey B.;Wassmer, Evangeline;Webb, Hannah J.;Whitehouse, William P.;Whitney, Robyn N.;Zaki, Maha S.;Zuberi, Sameer M.;Livingston, John H.;Rozenberg, Flore;Lebon, Pierre;Vanderver, Adeline;Orcesi, Simona;Rice, Gillian I.
通讯作者：
Rice, Gillian I.
DOI：
10.1111/j.1749-6632.2011.06220.x
发表时间：
2011-01-01
期刊：
YEAR IN HUMAN AND MEDICAL GENETICS: INBORN ERRORS OF IMMUNITY I
影响因子：
--
作者：
Crow, Yanick J.
通讯作者：
Crow, Yanick J.