<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1688-1249</journal-id>
<journal-title><![CDATA[Archivos de Pediatría del Uruguay]]></journal-title>
<abbrev-journal-title><![CDATA[Arch. Pediatr. Urug.]]></abbrev-journal-title>
<issn>1688-1249</issn>
<publisher>
<publisher-name><![CDATA[Sociedad Uruguaya de Pediatría]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1688-12492020000200084</article-id>
<article-id pub-id-type="doi">10.31134/ap.91.2.3</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Inversión de los intrones 1 y 22 del F8 en pacientes con hemofilia A severa y portadoras del noreste de Uruguay]]></article-title>
<article-title xml:lang="en"><![CDATA[F8 intron 1 and 22 inversions in patients with severe haemophilia A and in carriers of the northeastern region of Uruguay]]></article-title>
<article-title xml:lang="pt"><![CDATA[Inversão dos introns 1 e 22 do F8 em pacientes com hemofilia A severa e portadoras do nordeste de Uruguai]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vega]]></surname>
<given-names><![CDATA[Yasser]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Faguaga]]></surname>
<given-names><![CDATA[María]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Abelleyro]]></surname>
<given-names><![CDATA[Martín]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Brasi]]></surname>
<given-names><![CDATA[Carlos De]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Bandinelli]]></surname>
<given-names><![CDATA[Eliane]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sans]]></surname>
<given-names><![CDATA[Mónica]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hidalgo]]></surname>
<given-names><![CDATA[Pedro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,UDELAR PDU Diversidad Genética Humana Centro Universitario Tacuarembó]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Uruguay</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Hospital Regional Tacuarembó Banco de Sangre ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="Af3">
<institution><![CDATA[,Academia Nacional de Medicina Instituto Investigaciones Hematológicas Mariano R. Castex Instituto Medicina Experimental (CONICET)]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad Federal Rio Grande do Sul Instituto Biociencias Depto. Genética]]></institution>
<addr-line><![CDATA[Porto Alegre RS]]></addr-line>
<country>Brazil</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,UDELAR Facultad de Humanidades y Ciencias de la Educación Depto. Antropología Biológica]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Uruguay</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>00</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>00</month>
<year>2020</year>
</pub-date>
<volume>91</volume>
<numero>2</numero>
<fpage>84</fpage>
<lpage>89</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_arttext&amp;pid=S1688-12492020000200084&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_abstract&amp;pid=S1688-12492020000200084&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_pdf&amp;pid=S1688-12492020000200084&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen: La hemofilia A (HA) es la coagulopatía ligada al cromosoma X más frecuente. Es causada por mutaciones en el gen del factor VIII (FVIII) de coagulación (F8). La HA puede ser severa cuando la actividad del FVIII es menor a 1% (FVIII: C&lt;1IU/dL). Casi la mitad de las HA severas son producidas por inversiones del F8, como la del intrón 1 (Inv1) y del intrón 22 (Inv22). Los pacientes con HA severa experimentan sus primeros sangrados generales entre los 9,7 - 10,9 meses, ocurriendo principalmente en las articulaciones. Se investigó la presencia de la Inv1 e Inv22 en la región noreste de Uruguay (departamentos de Tacuarembó, Rivera y Cerro Largo) para estimar su frecuencia y detectar la presencia de portadoras. Fueron estudiados 14 individuos (ocho pacientes con HA severa, cuatro madres y dos hermanas de pacientes) de cinco familias. La investigación de las inversiones se realizó aplicando las pruebas de inverse shifting-PCR (IS-PCR). La Inv1 se encontró en dos pacientes (hermanos) de Tacuarembó, en su hermana y madre (portadoras), mientras que un paciente de Rivera y su madre (portadora) resultaron positivos para la Inv22. Preliminarmente, en conjunto, la Inv1 y la Inv22 representan la causa de la HA severa en el 40% de las familias del noreste de Uruguay, valor menor a lo esperado; sin embargo, debido a la reducida población estudiada, la Inv1 muestra una frecuencia preliminar (20%, 1/5 familias, 25%, 2/8 pacientes) considerablemente mayor a estudios previos. Estos datos permiten caracterizar la etiología genética de la hemofilia, la detección de las portadoras, conocer la distribución geográfica de las mutaciones y el asesoramiento genético.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Summary: Hemophilia A (HA) is the most common X-linked coagulopathy, it is caused by mutations in the coagulation factor VIII (FVIII) gene (F8). HA can be severe when the FVIII activity is less than 1% (FVIII: C &lt;1IU / dL). Almost a half of the severe HAs are produced by inversions of F8, the intron 1 (Inv1) and intron 22 (Inv22). Patients with severe HA show their first general bleeding between 9.7 - 10.9 months, mainly in the joints. We researched the presence of Inv1 and Inv22 in the Northeast region of Uruguay (Departments: Tacuarembó, Rivera and Cerro Largo) to estimate their frequency and detect the presence of carriers. We studied 14 individuals in 5 different families (8 patients with severe HA, 4 mothers and 2 sisters of patients). The inversion study was carried out using inverse shifting-PCR (IS-PCR) tests. Inv1 was found in 2 patients (siblings) from Tacuarembó, in their sister and mother (carriers). A patient from Rivera and his mother (carrier) were positive for Inv22. Inv1 and Inv22 are the cause of severe HA in 40% of the patients in North East of Uruguay, less than expected; however, due to the reduced population studied, Inv1 shows a considerably higher frequency than previous studies. These data enable us to characterize the genetic etiology of hemophilia, to adequately monitor patients, detect carriers, the geographical distribution of mutations and the corresponding genetic counseling for families.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Resumo: A hemofilia A (HA) é a coagulopatia ligada ao cromossomo X mais frequente, causada por mutações no gene do fator VIII (FVIII) de coagulação (FVIII) (F8). A HA pode ser grave quando a atividade do FVIII é menor que 1% (FVIII: C &lt;1IU / dL). Quase metade da HA grave é produzida por inversões de F8, como a do Íntron 1 (Inv1) e do Íntron 22 (Inv22). Pacientes com HA grave experimentam seu primeiro sangramento geral entre 9,7 e 10,9 meses, principalmente nas articulações. A presença de Inv1 e Inv22 na região nordeste do Uruguai (departamentos: Tacuarembó, Rivera e Cerro Largo) foi investigada para estimar a sua frequência e detectar a presença de portadora. Foram estudados 14 indivíduos (8 pacientes com HA grave, 4 mães e 2 irmãs de pacientes) de 5 famílias. A pesquisa das inversões foi realizada aplicando os testes de inverse shifting -PCR (IS-PCR). Encontramos Inv1 em 2 pacientes (irmãos) de Tacuarembó, na sua irmã e mãe (portadoras), enquanto 1 paciente de Rivera e sua mãe (transportadora) foram positivos para Inv22. Preliminarmente, Inv1 e Inv22 juntos representam a causa de HA grave em 40% das famílias do nordeste do Uruguai, valor inferior ao esperado, no entanto, devido à pequena população estudada, Inv1 mostra uma frequência preliminar (20%, 1/5 famílias, 25%, 2/8 pacientes) consideravelmente mais alta que os estudos anteriores. Esses dados permitem-nos caracterizar a etiologia genética da hemofilia, detectar aos portadores, conhecer a distribuição geográfica das mutações e realizar aconselhamento genético.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Hemofilia A]]></kwd>
<kwd lng="es"><![CDATA[Factor VIII]]></kwd>
<kwd lng="es"><![CDATA[Intrones]]></kwd>
<kwd lng="es"><![CDATA[Pruebas genéticas]]></kwd>
<kwd lng="en"><![CDATA[Hemophilia A]]></kwd>
<kwd lng="en"><![CDATA[Factor VIII]]></kwd>
<kwd lng="en"><![CDATA[Introns]]></kwd>
<kwd lng="en"><![CDATA[Genetic testing]]></kwd>
<kwd lng="pt"><![CDATA[Hemofilia A]]></kwd>
<kwd lng="pt"><![CDATA[Fator VIII]]></kwd>
<kwd lng="pt"><![CDATA[Íntrons]]></kwd>
<kwd lng="pt"><![CDATA[Testes genéticos]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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