A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy

被引：38

作者：

Horvath, Rita ^{[1
,2
]}

Holinski-Feder, Elke ^{[2
]}

Neeve, Vivienne C. M. ^{[1
]}

Pyle, Angela ^{[1
]}

Griffin, Helen ^{[1
]}

Ashok, Deephthi ^{[1
]}

Foley, Charlotte ^{[1
]}

Hudson, Gavin ^{[1
]}

Rautenstrauss, Bernd ^{[2
]}

Nuernberg, Gudrun ^{[3
,4
,5
]}

Nuernberg, Peter ^{[3
,4
,5
]}

Kortler, Joerg ^{[2
]}

Neitzel, Birgit ^{[2
]}

Baessmann, Ingelore ^{[3
]}

Rahman, Thahira ^{[1
]}

Keavney, Bernard ^{[1
]}

Loughlin, John ^{[6
]}

Hambleton, Sophie ^{[6
]}

Schoser, Benedikt ^{[7
]}

Lochmueller, Hanns ^{[1
]}

Santibanez-Koref, Mauro ^{[1
]}

Chinnery, Patrick F. ^{[1
]}

机构：

[1] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[2] Med Genet Ctr Munich, Munich, Germany

[3] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany

[4] Univ Cologne, CMMC, D-50931 Cologne, Germany

[5] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

[6] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[7] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-8000 Munich, Germany

来源：

MOVEMENT DISORDERS | 2012年 / 27卷 / 06期

基金：

英国医学研究理事会;

关键词：

neurodegeneration with brain iron accumulation (NBIA); dystonia; peripheral neuropathy; C19orf12; NEURODEGENERATION; MUTATION; PROTEIN; PLA2G6; FORM;

D O I：

10.1002/mds.24980

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes. Methods: We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family. Results: We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism. Conclusions: Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease. (C) 2012 Movement Disorder Society

引用

页码：789 / 793

页数：5

共 14 条

[1] Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease [J].

Curtis, ARJ ;

Fey, C ;

Morris, CM ;

Bindoff, LA ;

Ince, PG ;

Chinnery, PF ;

Coulthard, A ;

Jackson, MJ ;

Jackson, AP ;

McHale, DP ;

Hay, D ;

Barker, WA ;

Markham, AF ;

Bates, D ;

Curtis, A ;

Burn, J .

NATURE GENETICS, 2001, 28 (04) :350-354

[2] Clinical features and natural history of neuroferritinopathy caused by the 458dupA FTL mutation [J].

Devos, David ;

Tchofo, P. Jissendi ;

Vuillaume, Isabelle ;

Destee, Alain ;

Batey, Stephanie ;

Burn, John ;

Chinnery, Patrick F. .

BRAIN, 2009, 132

[3]

Gregory A., 1993, GENEREVIEWS

[4] Genetics of Neurodegeneration with Brain Iron Accumulation [J].

Gregory, Allison ;

Hayflick, Susan J. .

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2011, 11 (03) :254-261

[5]

Grisoli M, 2005, AM J NEURORADIOL, V26, P657

[6] Absence of an Orphan Mitochondrial Protein, C19orf12, Causes a Distinct Clinical Subtype of Neurodegeneration with Brain Iron Accumulation [J].

Hartig, Monika B. ;

Iuso, Arcangela ;

Haack, Tobias ;

Kmiec, Tomasz ;

Jurkiewicz, Elzbieta ;

Heim, Katharina ;

Roeber, Sigrun ;

Tarabin, Victoria ;

Dusi, Sabrina ;

Krajewska-Walasek, Malgorzata ;

Jozwiak, Sergiusz ;

Hempel, Maja ;

Winkelmann, Juliane ;

Elstner, Matthias ;

Oexle, Konrad ;

Klopstock, Thomas ;

Mueller-Felber, Wolfgang ;

Gasser, Thomas ;

Trenkwalder, Claudia ;

Tiranti, Valeria ;

Kretzschmar, Hans ;

Schmitz, Gerd ;

Strom, Tim M. ;

Meitinger, Thomas ;

Prokisch, Holger .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 89 (04) :543-550

[7] Defective FA2H Leads to a Novel Form of Neurodegeneration with Brain Iron Accumulation (NBIA) [J].

Kruer, Michael C. ;

Paisan-Ruiz, Coro ;

Boddaert, Nathalie ;

Yoon, Moon Y. ;

Hama, Hiroko ;

Gregory, Allison ;

Malandrini, Alessandro ;

Woltjer, Randall L. ;

Munnich, Arnold ;

Gobin, Stephanie ;

Polster, Brenda J. ;

Palmeri, Silvia ;

Edvardson, Simon ;

Hardy, John ;

Houlden, Henry ;

Hayflick, Susan J. .

ANNALS OF NEUROLOGY, 2010, 68 (05) :611-618

[8] T2*and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation [J].

McNeill, A. ;

Birchall, D. ;

Hayflick, S. J. ;

Gregory, A. ;

Schenk, J. F. ;

Zimmerman, E. A. ;

Shang, H. ;

Miyajima, H. ;

Chinnery, P. F. .

NEUROLOGY, 2008, 70 (18) :1614-1619

[9] PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron [J].

Morgan, Neil V. ;

Westaway, Shawn K. ;

Morton, Jenny E. V. ;

Gregory, Allison ;

Gissen, Paul ;

Sonek, Scott ;

Cangul, Hakan ;

Coryell, Jason ;

Canham, Natalie ;

Nardocci, Nardo ;

Zorzi, Giovanna ;

Pasha, Shanaz ;

Rodriguez, Diana ;

Desguerre, Isabelle ;

Mubaidin, Amar ;

Bertini, Enrico ;

Trembath, Richard C. ;

Simonati, Alessandro ;

Schanen, Carolyn ;

Johnson, Colin A. ;

Levinson, Barbara ;

Woods, C. Geoffrey ;

Wilmot, Beth ;

Kramer, Patricia ;

Gitschier, Jane ;

Maher, Eamonn R. ;

Hayflick, Susan J. .

NATURE GENETICS, 2006, 38 (07) :752-754

[10] Characterization of PLA2G6 as a Locus for Dystonia-Parkinsonism [J].

Paisan-Ruiz, Coro ;

Bhatia, Kailash P. ;

Li, Abi ;

Hernandez, Dena ;

Davis, Mary ;

Wood, Nick W. ;

Hardy, John ;

Houlden, Henry ;

Singleton, Andrew ;

Schneider, Susanne A. .

ANNALS OF NEUROLOGY, 2009, 65 (01) :19-23

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