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

被引:0
作者
Elena Martín-Hernández
María Elena Rodríguez-García
Ana Camacho
Antoni Matilla-Dueñas
María Teresa García-Silva
Pilar Quijada-Fraile
Marc Corral-Juan
Pilar Tejada-Palacios
Rogelio Simón de Las Heras
Joaquín Arenas
Miguel A. Martín
Francisco Martínez-Azorín
机构
[1] Hospital 12 de Octubre,Unidad de Enfermedades Mitocondriales y Enfermedades Metabólicas Hereditarias, Departamento de Pediatría
[2] Universidad Complutense de Madrid,Laboratorio de Enfermedades Mitocondriales
[3] Instituto de Investigación Hospital 12 de Octubre (IIS i+12),Unidad de Neuropediatría
[4] Hospital 12 de Octubre,Unidad de Neurogenética Funcional y Traslacional
[5] Instituto de Investigación en Ciencias de la Salud Germans Trias (IGTP),Departamento de Oftalmología
[6] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER),undefined
[7] U723,undefined
[8] Hospital 12 de Octubre,undefined
来源
neurogenetics | 2016年 / 17卷
关键词
Wes; Encephalopathy; Severe hypotonia; Chorea; Optic atrophy;
D O I
暂无
中图分类号
学科分类号
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
收藏
页码:259 / 263
页数:4
相关论文
共 102 条
[1]  
Calvo SE(2010)High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency Nat Genet 42 851-858
[2]  
Tucker EJ(2013)Whole-exome sequencing identifies a variant of the mitochondrial MT-ND1 gene associated with epileptic encephalopathy: west syndrome evolving to Lennox-Gastaut syndrome Hum Mutat 34 1623-1627
[3]  
Compton AG(2010)Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced translocation and a severe neurological phenotype Eur J Hum Genet 18 1360-1363
[4]  
Kirby DM(2009)Localization, purification, and functional reconstitution of the P4-ATPase Atp8a2, a phosphatidylserine flippase in photoreceptor disc membranes J Biol Chem 284 32670-32679
[5]  
Crawford G(2013)Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion Eur J Hum Genet 21 281-285
[6]  
Burtt NP(2012)Mutations in a P-type ATPase gene cause axonal degeneration PLoS Genet 8 e1002853-17216
[7]  
Rivas M(2011)Critical role of the beta-subunit CDC50A in the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2 J Biol Chem 286 17205-1812
[8]  
Guiducci C(2012)P4-ATPase ATP8A2 acts in synergy with CDC50A to enhance neurite outgrowth FEBS Lett 586 1803-1149
[9]  
Bruno DL(2014)Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival J Cell Sci 127 1138-266
[10]  
Goldberger OA(2011)P-type ATPases Annu Rev Biophys 40 243-3318