Diagnóstico molecular por reacción en cadena de la polimerasa del síndrome X frágil: aplicación de un protocolo diagnóstico en 50 familias del norte de España
Molecular diagnosis of fragile X syndrome by polymerase chain reaction: Application of a diagnostic protocol in 50 families from northern Spain
M. Durán Domíngueza,b, M. Molina Carrilloa, J. Fernández Toralc, T. Martínez Merinod, M.aA. López Arísteguie, A.I. Álvarez Retuertoa, M.aL. Onaindía Urquijoa, M.aI. Tejada Míngueza,
Autor para correspondencia
itejada@hbas.osakidetza.net
Correspondencia: Unidad de Genética. Hospital de Basurto. Avda. Montevideo, 18. 48013Bilbao
Correspondencia: Unidad de Genética. Hospital de Basurto. Avda. Montevideo, 18. 48013Bilbao
a Unidad de Genética. Hospital de Basurto. Bilbao.
b Instituto de Biología y Genética Molecular. Facultad de Medicina. Universidad de Valladolid.
c Sección de Genética. Servicio de Pediatría. Hospital Central de Asturias.
d Laboratorio de Genética. Hospital de Cantabria. Santander.
e Laboratorio de Genética. Hospital de Cruces. Baracaldo. Bilbao.
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Montevideo, 18. 48013Bilbao" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Molecular diagnosis of fragile X syndrome by polymerase chain reaction: Application of a diagnostic protocol in 50 families from northern Spain" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2000-03-31" "fechaAceptado" => "2000-11-30" "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec186635" "palabras" => array:4 [ 0 => "Síndrome X frágil" 1 => "Triplete CGG" 2 => "PCR" 3 => "Microsatélite DXS548" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec186634" "palabras" => array:4 [ 0 => "Fragile X syndrome" 1 => "CGG repeat" 2 => "Polymerase chain reaction" 3 => "DXS548microsatellite" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Poner a punto una metodología rápida y eficaz para el diagnóstico molecular del síndrome X frágil (SXF), mediante técnicas de reacción en cadena de la polimerasa (PCR) del triplete CGG, y establecer así un protocolo que nos sirva para: a) descartar el síndrome en pacientes con retraso mental no clasificado; b)averiguar el genotipo exacto de los individuos afectados; c)estudiar todos los individuos en riesgo de las familias con síndrome X frágil y encontrar los portadores asintomáticos, y d) proporcionar así el adecuado asesoramiento genético y reproductor a las familias en las que se transmita el síndrome.</p> <span class="elsevierStyleSectionTitle">Pacientes y métodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 438 muestras de individuos de 50 familias con síndrome X frágil. Se utilizaron tres protocolos de PCR, uno para detección con bromuro de etidio y luz ultravioleta; el segundo para detección con digoxigenina y el sustrato quimioluminiscente (CSPD), trasblotting e hibridación con la oligosonda (CGG)5; el tercero para amplificar y detectar de forma parecida el microsatélite DXS 548.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se encontraron 121 individuos con la mutación completa (60 varones y 61 mujeres); 86 premutados (7 varones y 79 mujeres); 16 mosaicos y 215 normales. La PCR ampli-ficó hasta 120-150 repeticiones, y fue necesario el estudio directo con sonda en el caso de ausencia de banda o banda única en mujeres. La PCR resultó más precisa que el Southern-blot de ADN genómico en los portadores premutados. Finalmente, se halló en una familia recombinación entre el locusFRAXA y el microsatélite DXS 548.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Estos protocolos de PCR no radiactiva permiten el diag-nóstico rápido y seguro del síndrome X frágil, y están especialmente indicados en posibles portadoras y para establecer el diagnóstico prenatal.</p>" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to develop a rapid, non-radioactive and effective method for the molecular diagnosis of fragile X syndrome (FXS) by the polymerase chain reaction (PCR) of the CGG repeat and to establish a protocol to be used in: a)ruling out FXS in patients with non-specific mental retardation; b) determining the exact genotype of affected individuals; c)studying all at-risk individuals from families with FXS and identifying asymptomatic carriers, and d) offering accurate genetic and reproductive counselling to families with FXS.</p> <span class="elsevierStyleSectionTitle">Materials and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Samples from 438 individuals from 50 families with FXS were studied using three different PCR tests: the first to detect ethidium bromide through ultraviolet light, the second to detect digoxigenin and CSPD after blotting and hybridisation with the (CGG)5 oligoprobe, and the third to amplify and detect the DXS 548 microsatellite.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Of the 438 individuals studied, 121 had full mutations (60 males and 61 females), 86 had pre-mutations (7 males and 79 females), 16 showed mosaic patterns and 215 had no mutations. PCR techniques amplified up to 120-150 repeats, and direct study with probes was required when no bands or only one band was detected in females. PCR was more accurate than genomic DNA Southern blot analysis in pre-mutated carriers. In one family, recombination between the FRAXA locus and the DXS 548 microsatellite was found.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">These non-radioactive PCR protocols permit rapid and accurate diagnosis of FXS. They and are especially useful in prenatal diagnosis and in the identification of carriers.</p>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara">Este trabajo ha sido financiado por un Proyecto de Investigación FIS (n. º 94/0857) y ayudas del Departamento de Sanidad del Gobierno Vasco</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F. Rousseau" 1 => "D. Heitz" 2 => "V. Biancalana" 3 => "S. Blumenfeld" 4 => "C. Kretz" 5 => "J. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 28 | 20 | 48 |
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| 2023 Enero | 27 | 30 | 57 |
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| 2022 Septiembre | 33 | 44 | 77 |
| 2022 Agosto | 70 | 50 | 120 |
| 2022 Julio | 50 | 44 | 94 |
| 2022 Junio | 54 | 33 | 87 |
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| 2022 Febrero | 40 | 26 | 66 |
| 2022 Enero | 58 | 53 | 111 |
| 2021 Diciembre | 53 | 56 | 109 |
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| 2021 Octubre | 78 | 73 | 151 |
| 2021 Septiembre | 42 | 49 | 91 |
| 2021 Agosto | 47 | 48 | 95 |
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| 2021 Junio | 56 | 34 | 90 |
| 2021 Mayo | 54 | 49 | 103 |
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| 2020 Diciembre | 57 | 19 | 76 |
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| 2020 Octubre | 35 | 47 | 82 |
| 2020 Septiembre | 53 | 28 | 81 |
| 2020 Agosto | 26 | 16 | 42 |
| 2020 Julio | 31 | 33 | 64 |
| 2020 Junio | 32 | 25 | 57 |
| 2020 Mayo | 39 | 31 | 70 |
| 2020 Abril | 35 | 19 | 54 |
| 2020 Marzo | 26 | 11 | 37 |
| 2020 Febrero | 36 | 31 | 67 |
| 2020 Enero | 31 | 42 | 73 |
| 2019 Diciembre | 28 | 46 | 74 |
| 2019 Noviembre | 19 | 37 | 56 |
| 2019 Octubre | 13 | 46 | 59 |
| 2019 Septiembre | 11 | 33 | 44 |
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| 2019 Mayo | 68 | 129 | 197 |
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| 2019 Marzo | 19 | 38 | 57 |
| 2019 Febrero | 18 | 20 | 38 |
| 2019 Enero | 14 | 16 | 30 |
| 2018 Diciembre | 13 | 13 | 26 |
| 2018 Noviembre | 25 | 26 | 51 |
| 2018 Octubre | 43 | 31 | 74 |
| 2018 Septiembre | 15 | 17 | 32 |
| 2018 Agosto | 3 | 0 | 3 |
| 2018 Julio | 2 | 0 | 2 |
| 2018 Mayo | 7 | 0 | 7 |
| 2018 Abril | 7 | 0 | 7 |
| 2018 Marzo | 12 | 0 | 12 |
| 2018 Febrero | 10 | 0 | 10 |
| 2018 Enero | 8 | 0 | 8 |
| 2017 Diciembre | 11 | 0 | 11 |
| 2017 Noviembre | 14 | 0 | 14 |
| 2017 Octubre | 15 | 0 | 15 |
| 2017 Septiembre | 14 | 0 | 14 |
| 2017 Agosto | 6 | 0 | 6 |
| 2017 Julio | 12 | 1 | 13 |
| 2017 Junio | 23 | 26 | 49 |
| 2017 Mayo | 20 | 14 | 34 |
| 2017 Abril | 14 | 21 | 35 |
| 2017 Marzo | 18 | 21 | 39 |
| 2017 Febrero | 13 | 24 | 37 |
| 2017 Enero | 7 | 5 | 12 |
| 2016 Diciembre | 23 | 17 | 40 |
| 2016 Noviembre | 45 | 11 | 56 |
| 2016 Octubre | 37 | 20 | 57 |
| 2016 Septiembre | 28 | 12 | 40 |
| 2016 Agosto | 43 | 14 | 57 |
| 2016 Julio | 26 | 17 | 43 |
| 2016 Junio | 1 | 0 | 1 |
| 2016 Mayo | 3 | 0 | 3 |
| 2016 Abril | 1 | 7 | 8 |
| 2016 Marzo | 6 | 0 | 6 |
| 2016 Febrero | 1 | 0 | 1 |
| 2016 Enero | 10 | 0 | 10 |
| 2015 Diciembre | 3 | 0 | 3 |
| 2015 Noviembre | 1 | 0 | 1 |
| 2015 Octubre | 5 | 7 | 12 |
| 2015 Septiembre | 1 | 0 | 1 |
| 2015 Agosto | 3 | 15 | 18 |
| 2015 Julio | 9 | 0 | 9 |
| 2015 Junio | 14 | 2 | 16 |
| 2015 Mayo | 12 | 0 | 12 |
| 2015 Abril | 14 | 12 | 26 |
| 2015 Marzo | 14 | 0 | 14 |
| 2015 Febrero | 12 | 8 | 20 |
| 2015 Enero | 23 | 1 | 24 |
| 2014 Diciembre | 29 | 5 | 34 |
| 2014 Noviembre | 18 | 1 | 19 |
| 2014 Octubre | 17 | 5 | 22 |
| 2014 Septiembre | 20 | 3 | 23 |
| 2014 Agosto | 34 | 4 | 38 |
| 2014 Julio | 34 | 3 | 37 |
| 2014 Junio | 59 | 3 | 62 |
| 2014 Mayo | 62 | 6 | 68 |
| 2014 Abril | 64 | 3 | 67 |
| 2014 Marzo | 52 | 6 | 58 |
| 2014 Febrero | 50 | 10 | 60 |
| 2014 Enero | 50 | 13 | 63 |
| 2013 Diciembre | 67 | 8 | 75 |
| 2013 Noviembre | 60 | 13 | 73 |
| 2013 Octubre | 67 | 27 | 94 |
| 2013 Septiembre | 35 | 11 | 46 |
| 2013 Agosto | 40 | 18 | 58 |
| 2013 Julio | 22 | 7 | 29 |
| 2013 Junio | 2 | 1 | 3 |
| 2013 Mayo | 5 | 2 | 7 |
| 2013 Abril | 2 | 6 | 8 |
| 2013 Marzo | 9 | 5 | 14 |
| 2013 Febrero | 32 | 2 | 34 |
| 2013 Enero | 11 | 1 | 12 |
| 2012 Diciembre | 8 | 1 | 9 |
| 2012 Noviembre | 9 | 4 | 13 |
| 2012 Octubre | 4 | 1 | 5 |
| 2012 Septiembre | 3 | 0 | 3 |
| 2012 Agosto | 4 | 0 | 4 |
| 2001 Marzo | 962 | 0 | 962 |
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