New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy

被引：37

作者：

Martin-Hernandez, Elena ^{[1
,2
]}

Elena Rodriguez-Garcia, Maria ^{[3
]}

Camacho, Ana ^{[4
]}

Matilla-Duenas, Antoni ^{[5
]}

Teresa Garcia-Silva, Maria ^{[1
,2
,6
]}

Quijada-Fraile, Pilar ^{[1
]}

Corral-Juan, Marc ^{[5
]}

Tejada-Palacios, Pilar ^{[7
]}

Simon de Las Heras, Rogelio ^{[4
]}

Arenas, Joaquin ^{[3
,6
]}

Martin, Miguel A. ^{[3
,6
]}

Martinez-Azorin, Francisco ^{[3
,6
]}

机构：

[1] Hosp 12 Octubre, Dept Pediat, Unidad Enfermedades Mitocondriales & Enfermedades, E-28041 Madrid, Spain

[2] Univ Complutense Madrid, E-28040 Madrid, Spain

[3] Hosp 12 Octubre IIS I 12, Inst Invest, Lab Enfermedades Mitocondriales, E-28041 Madrid, Spain

[4] Hosp 12 Octubre, Unidad Neuropediat, E-28041 Madrid, Spain

[5] Inst Invest Ciencias Salud Germans Trias IGTP, Unidad Neurogenet Func & Traslac, E-08916 Badalona, Spain

[6] CIBERER, U723, E-28041 Madrid, Spain

[7] Hosp 12 Octubre, Dept Oftalmol, E-28041 Madrid, Spain

来源：

NEUROGENETICS | 2016年 / 17卷 / 04期

关键词：

Wes; ATP8A2; Encephalopathy; Severe hypotonia; Chorea; Optic atrophy; QUADRUPEDAL LOCOMOTION; TRANSPORT ACTIVITY; P-4-ATPASE ATP8A2; CDC50A;

D O I：

10.1007/s10048-016-0496-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report the clinical and biochemical findings from two unrelated patients who presented with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Whole exome sequencing (WES) uncovered a homozygous mutation in the ATP8A2 gene (NM_016529:c.1287G > T, p.K429N) in one patient and compound heterozygous mutations (c.1630G > C, p.A544P and c.1873C > T, p.R625W) in the other. Only one haploinsufficiency case and a family with a homozygous mutation in ATP8A2 gene (c.1128C > G, p.I376M) have been described so far, with phenotypes that differed slightly from the patients described herein. In conclusion, our data expand both the genetic and phenotypic spectrum associated with ATP8A2 gene mutations.

引用

页码：259 / 263

页数：5

共 14 条

[1] Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced translocation and a severe neurological phenotype [J].

Cacciagli, Pierre ;

Haddad, Marie-Reine ;

Mignon-Ravix, Cecile ;

El-Waly, Bilal ;

Moncla, Anne ;

Missirian, Chantal ;

Chabrol, Brigitte ;

Villard, Laurent .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2010, 18 (12) :1360-1363

[2] High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency [J].

Calvo, Sarah E. ;

Tucker, Elena J. ;

Compton, Alison G. ;

Kirby, Denise M. ;

Crawford, Gabriel ;

Burtt, Noel P. ;

Rivas, Manuel ;

Guiducci, Candace ;

Bruno, Damien L. ;

Goldberger, Olga A. ;

Redman, Michelle C. ;

Wiltshire, Esko ;

Wilson, Callum J. ;

Altshuler, David ;

Gabriel, Stacey B. ;

Daly, Mark J. ;

Thorburn, David R. ;

Mootha, Vamsi K. .

NATURE GENETICS, 2010, 42 (10) :851-+

[3] Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival [J].

Coleman, Jonathan A. ;

Zhu, Xianjun ;

Djajadi, Hidayat R. ;

Molday, Laurie L. ;

Smith, Richard S. ;

Libby, Richard T. ;

John, Simon W. M. ;

Molday, Robert S. .

JOURNAL OF CELL SCIENCE, 2014, 127 (05) :1138-1149

[4] Critical Role of the β-Subunit CDC50A in the Stable Expression, Assembly, Subcellular Localization, and Lipid Transport Activity of the P4-ATPase ATP8A2 [J].

Coleman, Jonathan A. ;

Molday, Robert S. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (19) :17205-17216

[5] Localization, Purification, and Functional Reconstitution of the P4-ATPase Atp8a2, a Phosphatidylserine Flippase in Photoreceptor Disc Membranes [J].

Coleman, Jonathan A. ;

Kwok, Michael C. M. ;

Molday, Robert S. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (47) :32670-32679

[6] Whole-Exome Sequencing Identifies a Variant of the Mitochondrial MT-ND1 Gene Associated with Epileptic Encephalopathy: West Syndrome Evolving to Lennox-Gastaut Syndrome [J].

Delmiro, Aitor ;

Rivera, Henry ;

Teresa Garcia-Silva, Maria ;

Garcia-Consuegra, Ines ;

Martin-Hernandez, Elena ;

Quijada-Fraile, Pilar ;

Simon de Las Heras, Rogelio ;

Moreno-Izquierdo, Ana ;

Angel Martin, Miguel ;

Arenas, Joaquin ;

Martinez-Azorin, Francisco .

HUMAN MUTATION, 2013, 34 (12) :1623-1627

[7] Transport through recycling endosomes requires EHD1 recruitment by a phosphatidylserine translocase [J].

Lee, Shoken ;

Uchida, Yasunori ;

Wang, Jiao ;

Matsudaira, Tatsuyuki ;

Nakagawa, Takatoshi ;

Kishimoto, Takuma ;

Mukai, Kojiro ;

Inaba, Takehiko ;

Kobayashi, Toshihide ;

Molday, Robert S. ;

Taguchi, Tomohiko ;

Arai, Hiroyuki .

EMBO JOURNAL, 2015, 34 (05) :669-688

[8] WABBLER-LETHAL MOUSE - AN ELECTRON MICROSCOPIC STUDY OF NERVOUS SYSTEM [J].

LUSE, SA ;

CHENARD, C ;

FINKE, EH .

ARCHIVES OF NEUROLOGY, 1967, 17 (02) :153-&

[9] MUTATION OF ASPARTIC ACID-351, LYSINE-352, AND LYSINE-515 ALTERS THE CA-2+ TRANSPORT ACTIVITY OF THE CA-2+-ATPASE EXPRESSED IN COS-1 CELLS [J].

MARUYAMA, K ;

MACLENNAN, DH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (10) :3314-3318

[10] Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion [J].

Onat, Onur Emre ;

Gulsuner, Suleyman ;

Bilguvar, Kaya ;

Basak, Ayse Nazli ;

Topaloglu, Haluk ;

Tan, Meliha ;

Tan, Uner ;

Gunel, Murat ;

Ozcelik, Tayfun .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2013, 21 (03) :281-285

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