<?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>1405-9940</journal-id>
<journal-title><![CDATA[Archivos de cardiología de México]]></journal-title>
<abbrev-journal-title><![CDATA[Arch. Cardiol. Méx.]]></abbrev-journal-title>
<issn>1405-9940</issn>
<publisher>
<publisher-name><![CDATA[Instituto Nacional de Cardiología Ignacio Chávez]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1405-99402020000200130</article-id>
<article-id pub-id-type="doi">10.24875/acme.m20000106</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Phenotype of definite familial hypercholesterolemia with negative genetic study in Argentina]]></article-title>
<article-title xml:lang="es"><![CDATA[Fenotipo de hipercolesterolemia familiar definitivo con estudio genético negativo en Argentina]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Corral]]></surname>
<given-names><![CDATA[Pablo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Bañares]]></surname>
<given-names><![CDATA[Virginia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sáenz]]></surname>
<given-names><![CDATA[Benjamín]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Zago]]></surname>
<given-names><![CDATA[Valeria]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sarobe]]></surname>
<given-names><![CDATA[Agustina]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[López]]></surname>
<given-names><![CDATA[Graciela]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Berg]]></surname>
<given-names><![CDATA[Gabriela]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Schreier]]></surname>
<given-names><![CDATA[Laura]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad FASTA Facultad de Medicina ]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Administración Nacional de Laboratorios e Institutos de Salud &#8220;Dr. Carlos Malbran&#8221; Centro Nacional de Genética Medica &#8220;Dr. Eduardo Castilla&#8221; Departamento de Genética Experimental]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad FASTA Facultad de Medicina Departamento de Investigación]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad de Buenos Aires Departamento de Bioquímica Clínica Laboratorio de Lípidos y Aterosclerosis, INFIBIOCUBA]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>06</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>06</month>
<year>2020</year>
</pub-date>
<volume>90</volume>
<numero>2</numero>
<fpage>130</fpage>
<lpage>136</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S1405-99402020000200130&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S1405-99402020000200130&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S1405-99402020000200130&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  Objective: Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score &gt; 8 points qualifies the patient as &#8220;definite&#8221; for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment.  Methods: In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score &gt; 8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c.  Results: Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score &gt; 8 did not show any genetic alteration.  Conclusions: We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen  Objetivo: La hipercolesterolemia familiar (HF) es una enfermedad monogénica asociada a variantes en los genes RLDL, APOB y PCSK9. El diagnóstico inicial se basa en criterios clínicos, como el de la red de clínica de lípidos holandesa (DLCN). Un puntaje &gt; 8 puntos califica al paciente como &#8220;definitivo&#8221; para diagnóstico de HF. La identificación de una variante en estos genes permite realizar el cribado en cascada familiar y caracterizar mejor al paciente en cuanto al pronóstico y el tratamiento.  Métodos: En el marco del Programa de Detección de HF en Argentina (Estudio Da Vinci) se evaluó a 246 pacientes hipercolesterolémicos, 21 con puntaje DLCN &gt; 8 (diagnóstico definitivo). Se estudió a estos pacientes con secuenciación de próxima generación para reconocer variantes genéticas, con un panel ampliado de 23 genes, sumado al análisis de grandes rearreglos y por último se aplicó un score poligénico de 10 SNP (polimorfismo de nucleótido único) relacionados con aumento del c-LDL.  Resultados: De los 21 pacientes, 10 presentaron variantes en RLDL, uno en APOB junto a APOE, uno en LIPC más puntaje poligénico elevado, dos pacientes con una deleción y una duplicación en RLDL y este último caso con una variante en LIPA. Es destacable que 6 de los 21 pacientes con puntaje DLCN &gt; 8 no mostraron ninguna alteración genética.  Conclusiones: El 28% de los pacientes con diagnóstico clínico definitivo de HF no evidenció alteración genética. Las posibles explicaciones de este resultado serían la presencia de mutaciones en nuevos genes, los efectos confundidores del ambiente sobre los genes o la interacción gen-gen y por último la imposibilidad de detectar variantes con la metodología actual disponible.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Familial hypercholesterolemia]]></kwd>
<kwd lng="en"><![CDATA[Genetic diagnosis]]></kwd>
<kwd lng="en"><![CDATA[Polygenic score]]></kwd>
<kwd lng="es"><![CDATA[Hipercolesterolemia Familiar]]></kwd>
<kwd lng="es"><![CDATA[Diagnóstico genético]]></kwd>
<kwd lng="es"><![CDATA[Score poligénico]]></kwd>
</kwd-group>
</article-meta>
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