TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features

被引：103

作者：

Balestrini, Simona ^{[1
,2
,3
]}

Milh, Mathieu ^{[4
]}

Castiglioni, Claudia ^{[5
]}

Luethy, Kevin ^{[6
,7
]}

Finelli, Mattea J. ^{[8
]}

Verstreken, Patrik ^{[6
,7
]}

Cardon, Aaron ^{[10
]}

Strazisar, Barbara Gnidovec ^{[11
]}

Holder, J. Lloyd ^{[10
]}

Lesca, Gaetan ^{[12
]}

Mancardi, Maria M. ^{[14
]}

Poulat, Anne L. ^{[13
]}

Repetto, Gabriela M. ^{[17
]}

Banka, Siddharth ^{[18
]}

Bilo, Leonilda ^{[19
]}

Birkeland, Laura E. ^{[20
]}

Bosch, Friedrich ^{[21
]}

Brockmann, Knut ^{[22
]}

Cross, J. Helen ^{[23
,24
]}

Doummar, Diane ^{[25
]}

Felix, Temis M. ^{[26
]}

Giuliano, Fabienne ^{[27
]}

Hori, Mutsuki ^{[28
]}

Huening, Irina ^{[29
]}

Kayserili, Hulia ^{[30
]}

Kini, Usha ^{[31
]}

Lees, Melissa M. ^{[32
,33
]}

Meenakshi, Girish ^{[34
,35
]}

Mewasingh, Leena ^{[36
]}

Pagnamenta, Alistair T. ^{[9
]}

Peluso, Silvio ^{[19
]}

Mey, Antje ^{[37
]}

Rice, Gregory M. ^{[20
]}

Rosenfeld, Jill A. ^{[38
]}

Taylor, Jenny C. ^{[9
]}

Troester, Matthew M. ^{[39
]}

Stanley, Christine M. ^{[40
]}

Ville, Dorothee ^{[13
]}

Walkiewicz, Magdalena ^{[38
]}

Falace, Antonio ^{[41
]}

Fassio, Anna ^{[42
]}

Lemke, Johannes R. ^{[43
]}

Biskup, Saskia ^{[44
]}

Tardif, Jessica ^{[45
]}

Ajeawung, Norbert F. ^{[45
]}

Tolun, Aslihan ^{[46
]}

Corbett, Mark ^{[47
,48
]}

Gecz, Jozef ^{[47
,48
]}

Afawi, Zaid ^{[49
]}

Howell, Katherine B. ^{[50
,51
,52
,53
]}

机构：

[1] NIHR Univ Coll London Hosp, Biomed Res Ctr, Dept Clin & Expt Epilepsy, UCL Inst Neurol, London, England

[2] Epilepsy Soc, Gerrards Cross, Bucks, England

[3] Polytech Univ Marche, Neurosci Dept, Ancona, Italy

[4] Aix Marseille Univ, INSERM, GMGF UMR S 910, Marseille, France

[5] Clin Las Condes, Dept Pediat, Child Neurol Unit, Santiago, Chile

[6] VIB Ctr Biol Dis, Lab Neuronal Commun, Leuven, Belgium

[7] Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium

[8] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 2JD, England

[9] Univ Oxford, Natl Inst Hlth Res Biomed Res Ctr, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England

[10] Baylor Coll Med, Dept Pediat, Div Neurol & Dev Neurosci, Houston, TX 77030 USA

[11] Univ Childrens Hosp, Dept Child Adolescent & Dev Neurol, Ljubljana, Slovenia

[12] Lyon Univ Hosp, Dept Med Genet, Lyon, France

[13] Lyon Univ Hosp, Dept Neuropediat, Lyon, France

[14] Inst G Gaslini, Head Neck & Neurosci Dept, Unit Child Neuropsychiat, Genoa, Italy

[15] Inst G Gaslini, Pediat Neurol & Muscular Dis Unit, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[16] Inst G Gaslini, Dept Neurosci, Neurogenet Lab, Genoa, Italy

[17] Univ Desarrollo, Fac Med, Ctr Genet & Genom, Santiago, Chile

[18] Univ Manchester, Manchester Ctr Genom Ctr Genet Med, Inst Human Dev, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England

[19] Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy

[20] Univ Wisconsin Madison, Madison, WI USA

[21] Childrens Hosp Furth, Dept Neuropediat, Furth, Germany

[22] Univ Gottingen, Fac Med, Interdisciplinary Pediat Ctr Children Dev Disabil, Gottingen, Germany

[23] UCL Inst Child Hlth, London, England

[24] Great Ormond St Hosp Children NHS Fdn Trust, London, England

[25] Hop Trousseau, AP HP, Serv Neuropediat, Paris, France

[26] Clin Hosp Porto Alegre, Med Genet Serv, Porto Alegre, RS, Brazil

[27] Nice Teaching Hosp, Dept Med Genet, Nice, France

[28] Toyohashi Municipal Hosp, Dept Pediat, Toyohashi, Aichi, Japan

[29] Univ Lubeck, Inst Humangenet, Lubeck, Germany

[30] Koc Univ Sch Med KUSoM, Dept Med Genet, Istanbul, Turkey

[31] Oxford Univ Hosp NHS Trust, Dept Clin Genet, Oxford, England

[32] Great Ormond St Hosp NHS Trust, North Thames Cleft Ctr, London, England

[33] Great Ormond St Hosp NHS Trust, Clin Genet Dept, London, England

[34] NKP Salve Inst Med Sci, Dept Pediat, Nagpur, Maharashtra, India

[35] Lata Mangeshkar Hosp, Nagpur, Maharashtra, India

[36] Imperial Coll Healthcare NHS Trust, Dept Paediat Neurol, London, England

[37] Braunschweig Hosp, Pediat Neurol, Braunschweig, Germany

[38] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[39] Phoenix Childrens Hosp, Div Pediat Neurol, Barrow Neurol Inst, Phoenix, AZ USA

[40] Courtagen Life Sci Inc, Woburn, MA USA

[41] INSERM, UMR901, Inst Neurobiol Mediterranee, Marseille, France

[42] Univ Genoa, Dept Expt Med, I-16126 Genoa, Italy

[43] Univ Leipzig, Inst Human Genet, D-04109 Leipzig, Germany

[44] CeGaT GmbH, Tubingen, Germany

[45] Univ Montreal, Dept Pediat, St Justine Hosp, Montreal, PQ H3C 3J7, Canada

[46] Bogazici Univ, Dept Mol Biol & Genet, Istanbul, Turkey

[47] Univ Adelaide, Neurogenet Program, Sch Med, Adelaide, SA 5005, Australia

[48] Univ Adelaide, Robinson Res Inst, Adelaide, SA 5005, Australia

[49] Tel Aviv Univ, Sackler Sch Med, Ramat Aviv, Israel

[50] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia

来源：

NEUROLOGY | 2016年 / 87卷 / 01期

基金：

加拿大健康研究院; 澳大利亚国家健康与医学研究理事会; 欧洲研究理事会; 英国惠康基金;

关键词：

INFANTILE MYOCLONIC EPILEPSY; DOORS SYNDROME; HEARING-LOSS; SIBLINGS; MUTATION; PROTEINS; NEURODEGENERATION; IMPAIRMENT; ACTIVATION; MATURATION;

D O I：

10.1212/WNL.0000000000002807

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective:To evaluate the phenotypic spectrum associated with mutations in TBC1D24.Methods:We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24).Results:Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function.Conclusions:TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.

引用

页码：77 / 85

页数：9

共 35 条

[21] Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis [J].

Liu, Kevin X. ;

Edwards, Benjamin ;

Lee, Sheena ;

Finelli, Mattea J. ;

Davies, Ben ;

Davies, Kay E. ;

Oliver, Peter L. .

BRAIN, 2015, 138 :1167-1181

[22] Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton [J].

Marat, Andrea L. ;

Ioannou, Maria S. ;

McPherson, Peter S. .

MOLECULAR BIOLOGY OF THE CELL, 2012, 23 (01) :163-175

[23] Novel Compound Heterozygous Mutations in TBC1D24 Cause Familial Malignant Migrating Partial Seizures of Infancy [J].

Milh, Mathieu ;

Falace, Antonio ;

Villeneuve, Nathalie ;

Vanni, Nicola ;

Cacciagli, Pierre ;

Assereto, Stefania ;

Nabbout, Rima ;

Benfenati, Fabio ;

Zara, Federico ;

Chabrol, Brigitte ;

Villard, Laurent ;

Fassio, Anna .

HUMAN MUTATION, 2013, 34 (06) :869-872

[24] A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy (vol 47, pg 39, 2015) [J].

Muona, Mikko ;

Berkovic, Samuel F. ;

Dibbens, Leanne M. ;

Oliver, Karen L. ;

Maljevic, Snezana ;

Bayly, Marta A. ;

Joensuu, Tarja ;

Canafoglia, Laura ;

Franceschetti, Silvana ;

Michelucci, Roberto ;

Markkinen, Salla ;

Heron, Sarah E. ;

Hildebrand, Michael S. ;

Andermann, Eva ;

Andermann, Frederick ;

Gambardella, Antonio ;

Tinuper, Paolo ;

Licchetta, Laura ;

Scheffer, Ingrid E. ;

Criscuolo, Chiara ;

Filla, Alessandro ;

Ferlazzo, Edoardo ;

Ahmad, Jamil ;

Ahmad, Adeel ;

Baykan, Betul ;

Said, Edith ;

Topcu, Meral ;

Riguzzi, Patrizia ;

King, Mary D. ;

Ozkara, Cigdem ;

Andrade, Danielle M. ;

Engelsen, Bernt A. ;

Crespel, Arielle ;

Lindenau, Matthias ;

Lohmann, Ebba ;

Saletti, Veronica ;

Massano, Joao ;

Privitera, Michael ;

Espay, Alberto J. ;

Kauffmann, Birgit ;

Duchowny, Michael ;

Moller, Rikke S. ;

Straussberg, Rachel ;

Afawi, Zaid ;

Ben-Zeev, Bruria ;

Samocha, Kaitlin E. ;

Daly, Mark J. ;

Petrou, Steven ;

Lerche, Holger ;

Palotie, Aarno .

NATURE GENETICS, 2015, 47 (01) :39-+

[25] Structural/functional analysis of the human OXR1 protein: identification of exon 8 as the anti-oxidant encoding function [J].

Murphy, Kenan C. ;

Volkert, Michael R. .

BMC MOLECULAR BIOLOGY, 2012, 13

[26] Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration [J].

Oliver, Peter L. ;

Finelli, Mattea J. ;

Edwards, Benjamin ;

Bitoun, Emmanuelle ;

Butts, Darcy L. ;

Becker, Esther B. E. ;

Cheeseman, Michael T. ;

Davies, Ben ;

Davies, Kay E. .

PLOS GENETICS, 2011, 7 (10)

[27] Homozygous TBC1D24 mutation in two siblings with familial infantile myoclonic epilepsy (FIME) and moderate intellectual disability [J].

Poulat, Anne-Lise ;

Ville, Dorothee ;

de Bellescize, Julitta ;

Andre-Obadia, Nathalie ;

Cacciagli, Pierre ;

Milh, Mathieu ;

Villard, Laurent ;

Lesca, Gaetan .

EPILEPSY RESEARCH, 2015, 111 :72-77

[28] ARF6-mediated endosomal transport of Telencephalin affects dendritic filopodia-to-spine maturation [J].

Raemaekers, Tim ;

Peric, Aleksandar ;

Baatsen, Pieter ;

Sannerud, Ragna ;

Declerck, Ilse ;

Baert, Veerle ;

Michiels, Christine ;

Annaert, Wim .

EMBO JOURNAL, 2012, 31 (15) :3252-3269

[29] Mutations in TBC1D24, a Gene Associated With Epilepsy, Also Cause Nonsyndromic Deafness DFNB86 [J].

Rehman, Atteeq U. ;

Santos-Cortez, Regie Lyn P. ;

Morell, Robert J. ;

Drummond, Meghan C. ;

Ito, Taku ;

Lee, Kwanghyuk ;

Khan, Asma A. ;

Basra, Muhammad Asim R. ;

Wasif, Naveed ;

Ayub, Muhammad ;

Ali, Rana A. ;

Raza, Syed I. ;

Nickerson, Deborah A. ;

Shendure, Jay ;

Bamshad, Michael ;

Riazuddin, Saima ;

Billington, Neil ;

Khan, Shaheen N. ;

Friedman, Penelope L. ;

Griffith, Andrew J. ;

Ahmad, Wasim ;

Riazuddin, Sheikh ;

Leal, Suzanne M. ;

Friedman, Thomas B. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2014, 94 (01) :144-152

[30] AMPA Receptor Signaling through BRAG2 and Arf6 Critical for Long-Term Synaptic Depression [J].

Scholz, Ralf ;

Berberich, Sven ;

Rathgeber, Louisa ;

Kolleker, Alexander ;

Koehr, Georg ;

Kornau, Hans-Christian .

NEURON, 2010, 66 (05) :768-780

← 1 2 3 4 →