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González-Morón, D.; Vishnopolska, S.; Consalvo, D.; Medina, N.; Marti, M.; Córdoba, M.; Vazquez-Dusefante, C.; Claverie, S.; Rodríguez-Quiroga, S.A.; Vega, P.; Silva, W.; Kochen, S.; Kauffman, M.A. "Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders" (2017) PLoS ONE. 12(9)
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Abstract:

Neuronal migration disorders are a clinically and genetically heterogeneous group of malformations of cortical development, frequently responsible for severe disability. Despite the increasing knowledge of the molecular mechanisms underlying this group of diseases, their genetic diagnosis remains unattainable in a high proportion of cases. Here, we present the results of 38 patients with lissencephaly, periventricular heterotopia and subcortical band heterotopia from Argentina. We performed Sanger and Next Generation Sequencing (NGS) of DCX, FLNA and ARX and searched for copy number variations by MLPA in PAFAH1B1, DCX, POMT1, and POMGNT1. Additionally, somatic mosaicism at 5% or higher was investigated by means of targeted high coverage NGS of DCX, ARX, and PAFAH1B1. Our approach had a diagnostic yield of 36%. Pathogenic or likely pathogenic variants were identified in 14 patients, including 10 germline (five novel) and 4 somatic mutations in FLNA, DCX, ARX and PAFAH1B1 genes. This study represents the largest series of patients comprehensively characterized in our population. Our findings reinforce the importance of somatic mutations in the pathophysiology and diagnosis of neuronal migration disorders and contribute to expand their phenotype-genotype correlations. © 2017 González-Morón et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Registro:

Documento: Artículo
Título:Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders
Autor:González-Morón, D.; Vishnopolska, S.; Consalvo, D.; Medina, N.; Marti, M.; Córdoba, M.; Vazquez-Dusefante, C.; Claverie, S.; Rodríguez-Quiroga, S.A.; Vega, P.; Silva, W.; Kochen, S.; Kauffman, M.A.
Filiación:Consultorio y laboratorio de Neurogenética, Centro Universitario de Neurología José María Ramos Mejía y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA, Buenos Aires, Argentina
IBCN Eduardo de Robertis, Facultad de Medicina, UBA-CONICET, Buenos Aires, Argentina
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina
CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina
Centro Universitario de Neurología José María Ramos Mejía y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA, Buenos Aires, Argentina
Sección Neurofisiología y Epilepsia, Consultorio de Epilepsias Refractarias, Servicio de Neurología Infantil, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Centro de Epilepsia, División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA, Buenos Aires, Argentina
Programa de Medicina de Precisión y Genómica Clínica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Derqui, Argentina
Palabras clave:alanine; arginine; cysteine; glycine; proline; serine; acidosis; agyria; ambiguous genitalia; amino acid sequence; amino acid substitution; Argentina; Article; ARX gene; brain malformation; chromosome breakage; clinical article; controlled study; copy number variation; corpus callosum agenesis; DCX gene; diagnostic value; diarrhea; disease association; disease severity; epilepsy; exon; family history; feasibility study; female; FLNA gene; frameshift mutation; gene; gene deletion; gene frequency; gene identification; gene insertion; gene targeting; genetic variability; genotype phenotype correlation; germline mutation; heart ventricle septum defect; heterozygosity; human; hypothermia; intellectual impairment; karyotype; macrogyria; male; missense mutation; mosaicism; mutational analysis; neuronal migration disorder; next generation sequencing; nonsense mutation; null allele; PAFAH1B1 gene; pathophysiology; periventricular heterotopia; personality disorder; point mutation; POMGNT1 gene; POMT1 gene; Sanger sequencing; septum pellucidum agenesis; sequence analysis; sex difference; somatic mutation; spontaneous abortion; stop codon; subcortical heterotopia; vermis hypoplasia; white matter lesion; X chromosome; cohort analysis; genetics; genotype; Malformations of Cortical Development, Group II; phenotype; young adult; Cohort Studies; DNA Copy Number Variations; Female; Genotype; Germ-Line Mutation; Humans; Male; Malformations of Cortical Development, Group II; Phenotype; Young Adult
Año:2017
Volumen:12
Número:9
DOI: http://dx.doi.org/10.1371/journal.pone.0185103
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:alanine, 56-41-7, 6898-94-8; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; cysteine, 4371-52-2, 52-89-1, 52-90-4; glycine, 56-40-6, 6000-43-7, 6000-44-8; proline, 147-85-3, 7005-20-1; serine, 56-45-1, 6898-95-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n9_p_GonzalezMoron

Referencias:

  • Guerrini, R., Parrini, E., Neuronal migration disorders (2010) Neurobiol Dis, 38 (2), pp. 154-166. , https://doi.org/10.1016/j.nbd.2009.02.008, Epub 2009/02/ 28. PMID: 19245832
  • Manzini, M.C., Walsh, C.A., What disorders of cortical development tell us about the cortex: One plus one does not always make two (2011) Current Opinion in Genetics & Development, 21 (3), pp. 333-339. , https://doi.org/10.1016/j.gde.2011.01.006, Epub 2011/ 02/04. PMID: 21288712
  • Parrini, E., Conti, V., Dobyns, W.B., Guerrini, R., Genetic Basis of Brain Malformations (2016) Molecular Syndromology, 7 (4), pp. 220-233. , https://doi.org/10.1159/000448639, Epub 2016/10/27. PMID: 27781032
  • Jamuar, S.S., Lam, A.T., Kircher, M., D’Gama, A.M., Wang, J., Barry, B.J., Somatic mutations in cerebral cortical malformations (2014) The New England Journal of Medicine, 371 (8), pp. 733-743. , https://doi.org/10.1056/NEJMoa1314432, Epub 2014/08/21. PMID: 25140959
  • Bahi-Buisson, N., Souville, I., Fourniol, F.J., Toussaint, A., Moores, C.A., Houdusse, A., New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum (2013) Brain, 136, pp. 223-244. , https://doi.org/10.1093/brain/aws323, Epub 2013/02/01. PMID: 23365099
  • Mandelstam, S.A., Leventer, R.J., Sandow, A., McGillivray, G., Van Kogelenberg, M., Guerrini, R., Bilateral posterior periventricular nodular heterotopia: A recognizable cortical malformation with a spectrum of associated brain abnormalities (2013) AJNR American Journal of Neuroradiology, 34 (2), pp. 432-438. , https://doi.org/10.3174/ajnr.A3427, Epub 2013/01/26. PMID: 23348762
  • Gonzalez, G., Vedolin, L., Barry, B., Poduri, A., Walsh, C., Barkovich, A.J., Location of periventricular nodular heterotopia is related to the malformation phenotype on MRI (2013) AJNR American Journal of Neuroradiology, 34 (4), pp. 877-883. , https://doi.org/10.3174/ajnr.A3312, Epub 2012/10/16. PMID: 23064591
  • Kauffman, M.A., Gonzlez-Moron, D., Consalvo, D., Westergaard, G., Vazquez, M., Mancini, E., Diagnosis of mitochondrial disorders applying massive pyrosequencing (2012) Molecular Biology Reports, 39 (6), pp. 6655-6660. , https://doi.org/10.1007/s11033-012-1471-9, Epub 2012/02/04. PMID: 22302390
  • De Wit, M.C., De Coo, I.F., Lequin, M.H., Halley, D.J., Roos-Hesselink, J.W., Mancini, G.M., Combined cardiological and neurological abnormalities due to filamin A gene mutation (2011) Clinical Research in Cardiology: Official Journal of The German Cardiac Society, 100 (1), pp. 45-50. , https://doi.org/10.1007/s00392-010-0206-y, Epub 2010/08/24. PMID: 20730588
  • DePristo, M.A., Banks, E., Poplin, R., Garimella, K.V., Maguire, J.R., Hartl, C., A framework for variation discovery and genotyping using next-generation DNA sequencing data (2011) Nat Genet, 43 (5), pp. 491-498. , https://doi.org/10.1038/ng.806, Epub 2011/04/12. PMID: 21478889
  • Van Der Auwera, G.A., Carneiro, M.O., Hartl, C., Poplin, R., Del Angel, G., Levy-Moonshine, A., From FastQ data to high confidence variant calls: The Genome Analysis Toolkit best practices pipeline (2013) Current Protocols in Bioinformatics, 43, pp. 1101-1133. , https://doi.org/10.1002/0471250953.bi1110s43, Epub 2014/11/29. PMID: 25431634
  • McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data (2010) Genome Res, 20 (9), pp. 1297-1303. , https://doi.org/10.1101/gr.107524.110, Epub 2010/07/21. PMID: 20644199
  • Rimmer, A., Phan, H., Mathieson, I., Iqbal, Z., Twigg, S.R., Consortium, W.G.S., Integrating mapping-, assembly- And haplotype-based approaches for calling variants in clinical sequencing applications (2014) Nat Genet, 46 (8), pp. 912-918. , https://doi.org/10.1038/ng.3036, Epub 2014/07/16. PMID: 25017105
  • Rausch, T., Zichner, T., Schlattl, A., Stutz, A.M., Benes, V., Korbel, J.O., DELLY: Structural variant discovery by integrated paired-end and split-read analysis (2012) Bioinformatics, 28 (18), pp. i333-i339. , https://doi.org/10.1093/bioinformatics/bts378, Epub 2012/09/11. PMID: 22962449
  • Cingolani, P., Platts, A., Wang le, L., Coon, M., Nguyen, T., Wang, L., A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3 (2012) Fly, 6 (2), pp. 80-92. , https://doi.org/10.4161/fly.19695, Epub 2012/06/26. PMID: 22728672
  • Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (2015) Genetics in Medicine: Official Journal of The American College of Medical Genetics, 17 (5), pp. 405-424. , https://doi.org/10.1038/gim.2015.30, Epub 2015/03/06. PMID: 25741868
  • Matsumoto, N., Leventer, R.J., Kuc, J.A., Mewborn, S.K., Dudlicek, L.L., Ramocki, M.B., Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia (2001) European Journal of Human Genetics: EJHG, 9 (1), pp. 5-12. , https://doi.org/10.1038/sj.ejhg.5200548, Epub 2001/02/15. PMID: 11175293
  • D’Agostino, M.D., Bernasconi, A., Das, S., Bastos, A., Valerio, R.M., Palmini, A., Subcortical band heterotopia (SBH) in males: Clinical, imaging and genetic findings in comparison with females (2002) Brain, 125, pp. 2507-2522. , Epub 2002/10/23. PMID: 12390976
  • Parrini, E., Ramazzotti, A., Dobyns, W.B., Mei, D., Moro, F., Veggiotti, P., Periventricular heterotopia: Phenotypic heterogeneity and correlation with Filamin A mutations (2006) Brain, 129, pp. 1892-1906. , https://doi.org/10.1093/brain/awl125, Epub 2006/05/11. PMID: 16684786
  • Ju, Y.S., Martincorena, I., Gerstung, M., Petljak, M., Alexandrov, L.B., Rahbari, R., Somatic mutations reveal asymmetric cellular dynamics in the early human embryo (2017) Nature, 543 (7647), pp. 714-718. , https://doi.org/10.1038/nature21703, Epub 2017/03/23. PMID: 28329761
  • Quelin, C., Saillour, Y., Souville, I., Poirier, K., N’Guyen-Morel, M.A., Vercueil, L., Mosaic DCX deletion causes subcortical band heterotopia in males (2012) Neurogenetics, 13 (4), pp. 367-373. , https://doi.org/10.1007/s10048-012-0339-4, Epub 2012/07/27. PMID: 22833188
  • Zillhardt, J.L., Poirier, K., Broix, L., Lebrun, N., Elmorjani, A., Martinovic, J., Mosaic parental germline mutations causing recurrent forms of malformations of cortical development (2016) European Journal of Human Genetics: EJHG, 24 (4), pp. 611-614. , https://doi.org/10.1038/ejhg.2015.192, Epub 2015/09/24. PMID: 26395554
  • Van Nimwegen, K.J., Van Soest, R.A., Veltman, J.A., Nelen, M.R., Van Der Wilt, G.J., Vissers, L.E., Is the $1000 Genome as Near as We Think? A Cost Analysis of Next-Generation Sequencing (2016) Clinical Chemistry, 62 (11), pp. 1458-1464. , https://doi.org/10.1373/clinchem.2016.258632, Epub 2016/10/30. PMID: 27630156
  • Qin, L., Wang, J., Tian, X., Yu, H., Truong, C., Mitchell, J.J., Detection and Quantification of Mosaic Mutations in Disease Genes by Next-Generation Sequencing (2016) The Journal of Molecular Diagnostics: JMD, 18 (3), pp. 446-453. , https://doi.org/10.1016/j.jmoldx.2016.01.002, Epub 2016/03/06. PMID: 26944031
  • Jamuar, S.S., Walsh, C.A., Genomic variants and variations in malformations of cortical development (2015) Pediatric Clinics of North America, 62 (3), pp. 571-585. , https://doi.org/10.1016/j.pcl.2015.03.002, Epub 2015/05/30. PMID: 26022163
  • Hertecant, J., Komara, M., Nagi, A., Suleiman, J., Al-Gazali, L., Ali, B.R., A novel de novo mutation in DYNC1H1 gene underlying malformation of cortical development and cataract (2016) Meta Gene, 9, pp. 124-127. , https://doi.org/10.1016/j.mgene.2016.05.004, Epub 2016/06/23. PMID: 27331017

Citas:

---------- APA ----------
González-Morón, D., Vishnopolska, S., Consalvo, D., Medina, N., Marti, M., Córdoba, M., Vazquez-Dusefante, C.,..., Kauffman, M.A. (2017) . Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders. PLoS ONE, 12(9).
http://dx.doi.org/10.1371/journal.pone.0185103
---------- CHICAGO ----------
González-Morón, D., Vishnopolska, S., Consalvo, D., Medina, N., Marti, M., Córdoba, M., et al. "Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders" . PLoS ONE 12, no. 9 (2017).
http://dx.doi.org/10.1371/journal.pone.0185103
---------- MLA ----------
González-Morón, D., Vishnopolska, S., Consalvo, D., Medina, N., Marti, M., Córdoba, M., et al. "Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders" . PLoS ONE, vol. 12, no. 9, 2017.
http://dx.doi.org/10.1371/journal.pone.0185103
---------- VANCOUVER ----------
González-Morón, D., Vishnopolska, S., Consalvo, D., Medina, N., Marti, M., Córdoba, M., et al. Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders. PLoS ONE. 2017;12(9).
http://dx.doi.org/10.1371/journal.pone.0185103