<?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>1688-0420</journal-id>
<journal-title><![CDATA[Revista Uruguaya de Cardiología]]></journal-title>
<abbrev-journal-title><![CDATA[Rev.Urug.Cardiol.]]></abbrev-journal-title>
<issn>1688-0420</issn>
<publisher>
<publisher-name><![CDATA[Sociedad Uruguaya de Cardiología]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1688-04202019000300239</article-id>
<article-id pub-id-type="doi">10.29277/cardio.34.3.21</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Genética de la hipercolesterolemia familiar]]></article-title>
<article-title xml:lang="en"><![CDATA[Genetics of familial hypercholesterolemia]]></article-title>
<article-title xml:lang="pt"><![CDATA[Genética da hipercolesterolemia familiar]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Stoll]]></surname>
<given-names><![CDATA[Mario]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Dell&#8217;Oca]]></surname>
<given-names><![CDATA[Nicolás]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Comisión Honoraria para la Salud Cardiovascular Laboratorio de Genética Molecular ]]></institution>
<addr-line><![CDATA[Montevideo ]]></addr-line>
<country>Uruguay</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2019</year>
</pub-date>
<volume>34</volume>
<numero>3</numero>
<fpage>239</fpage>
<lpage>259</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_arttext&amp;pid=S1688-04202019000300239&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_abstract&amp;pid=S1688-04202019000300239&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_pdf&amp;pid=S1688-04202019000300239&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen: La hipercolesterolemia familiar (HF) es un trastorno hereditario caracterizado por niveles séricos anormalmente altos de colesterol desde el nacimiento. Por este motivo, los pacientes con HF presentan un riesgo muy alto de sufrir eventos cardiovasculares prematuros. Con una prevalencia de 1 en 250, la HF es considerada hoy día una de las enfermedades genéticas más frecuentes en la población mundial. Sin embargo, a pesar de su elevada frecuencia y de que existen tratamientos efectivos para controlarla, la HF continúa siendo subtratada y subdiagnosticada. La HF es un trastorno oligogénico del metabolismo lipídico determinado principalmente por mutaciones en el gen LDLR (90% de los casos) y de herencia autosómica dominante. Con menos frecuencia se han encontrado mutaciones en genes APOB, PCSK9, STAP1 y APOE (también de herencia autosómica dominante) y en el gen LDLRAP1 (de herencia autosómica recesiva). En los pacientes sin mutaciones en estos genes, el aumento del colesterol puede ser explicado por la suma de alelos de riesgo en distintos loci, configurando una HF poligénica. Esta diversidad de mutaciones mayores y variantes comunes polimórficas conduce a un amplio espectro de presentaciones clínicas. La presencia de mutaciones en el gen LDLR aumenta más de veinte veces el riesgo de sufrir eventos coronarios. La identificación de una variante patogénica permite iniciar el diagnóstico familiar en cascada, que es la estrategia más costo-efectiva para la identificación de afectados. Es por esto que en los últimos años se ha destacado la importancia del diagnóstico molecular como conductor de la intervención médica y del seguimiento familiar.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Summary: Familial hypercholesterolemia is an inherited disorder characterized by abnormally high serum cholesterol levels from birth. For this reason, patients have a very high risk of suffering premature cardiovascular events. With a prevalence of 1 in 250, it is now considered one of the most frequent genetic diseases in the world. However, despite its high frequency and effective treatments, it continues to be under-treated and under-diagnosed worldwide. Familial hypercholesterolemia is an oligogenic disorder of lipid metabolism mainly determined by mutations in LDLR gene (90% of cases) and of autosomal dominant inheritance. Less frequently, mutations have been found in APOB, PCSK9, STAP1 and APOE genes (also of autosomal dominant inheritance) and in the LDLRAP1 gene (of autosomal recessive inheritance). In patients without mutations in these genes, the increase in their cholesterol can be explained by the sum of risk alleles in different loci, configuring a polygenic disease. This diversity of major mutations and common polymorphic variants lead to a wide spectrum of clinical presentations. The presence of mutations in the LDLR gene increases the risk of coronary events over twenty times. The identification of a pathogenic variant allows family cascade screening, which is the most cost-effective strategy for the identification of affected persons. That is why in recent years the importance of molecular diagnosis as a driver of medical intervention and family monitoring has been highlighted.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Resumo: A hipercolesterolemia familiar é um distúrbio hereditário caracterizado por níveis séricos de colesterol anormalmente altos desde o nascimento. Por esse motivo, os pacientes apresentam um risco muito alto de sofrer eventos cardiovasculares prematuros. Com prevalência de 1 em 250, é hoje considerada uma das doenças genéticas mais frequentes na população mundial. No entanto, apesar de sua alta frequência e da existência de tratamentos eficazes para controlá-la, ela continua sendo subtratada e subdiagnosticada em todo o mundo. É um distúrbio oligogênico do metabolismo lipídico, determinado principalmente por mutações no gene LDLR (90% dos casos) e herança autossômica dominante. Menos frequentemente, foram encontradas mutações nos genes APOB, PCSK9, STAP1 e APOE (também de herança autossômica dominante) e no gene LDLRAP1 (de herança autossômica recessiva). Em pacientes sem mutações nesses genes, o aumento do colesterol pode ser explicado pela soma dos alelos de risco em diferentes loci, configurando uma hipercolesterolemia familiar poligênica. Essa diversidade de grandes mutações e variantes polimórficas comuns leva a um amplo espectro de apresentações clínicas. A presença de mutações no gene LDLR aumenta o risco de eventos coronarianos mais de vinte vezes. A identificação de uma variante patogênica permite iniciar o diagnóstico da família em cascata, que é a estratégia mais econômica para a identificação das pessoas afetadas. É por isso que, nos últimos anos, foi destacada a importância do diagnóstico molecular como fator de intervenção médica e monitoramento familiar.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Hiperlipoproteinemia Tipo II]]></kwd>
<kwd lng="es"><![CDATA[Prevención primaria]]></kwd>
<kwd lng="es"><![CDATA[Diagnóstico molecular]]></kwd>
<kwd lng="en"><![CDATA[Type II hyperlipoproteinemia]]></kwd>
<kwd lng="en"><![CDATA[Primary prevention]]></kwd>
<kwd lng="en"><![CDATA[Molecular diagnostic]]></kwd>
<kwd lng="pt"><![CDATA[Hiperlipoproteinemia Tipo II]]></kwd>
<kwd lng="pt"><![CDATA[Prevenção primária]]></kwd>
<kwd lng="pt"><![CDATA[Diagnóstico molecular]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="book">
<collab>World Health Organization</collab>
<source><![CDATA[Human genetics Programme. Familial hypercholesterolaemia (FH): report of a second WHO Consultation, Geneva, 4 September 1998]]></source>
<year>1999</year>
<publisher-loc><![CDATA[Geneva ]]></publisher-loc>
<publisher-name><![CDATA[WHO]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Nordestgaard]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Chapman]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Humphries]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Ginsberg]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Masana]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Descamps]]></surname>
<given-names><![CDATA[O]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society]]></article-title>
<source><![CDATA[Eur Heart J]]></source>
<year>2013</year>
<volume>34</volume>
<numero>45</numero>
<issue>45</issue>
<page-range>3478-90a</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Müller]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Xanthomata, hypercholesterolemia, angina pectoris]]></article-title>
<source><![CDATA[J Intern Med]]></source>
<year>1938</year>
<volume>95</volume>
<numero>S89</numero>
<issue>S89</issue>
<page-range>75-84</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Marenberg]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Risch]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Berkman]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Flodeurs]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[de Faire]]></surname>
<given-names><![CDATA[U]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Genetic suceptibility to death from coronary heart disease in a study of twins]]></article-title>
<source><![CDATA[N Engl J Med]]></source>
<year>1994</year>
<volume>330</volume>
<page-range>1041-6</page-range></nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Scheuner]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Whitworth]]></surname>
<given-names><![CDATA[W]]></given-names>
</name>
<name>
<surname><![CDATA[McGruder]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Yoon]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Khoury]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Familial risk assessment for early-onset coronary heart disease]]></article-title>
<source><![CDATA[Genet Med]]></source>
<year>2006</year>
<volume>8</volume>
<numero>8</numero>
<issue>8</issue>
<page-range>525-31</page-range></nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Stoll]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Raggio]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[La historia familiar: el primer paso a la genómica médica]]></article-title>
<source><![CDATA[Tendencias]]></source>
<year>2007</year>
<volume>15</volume>
<numero>30</numero>
<issue>30</issue>
<page-range>117-23</page-range></nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Khera]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Won]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Peloso]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Lawson]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Bartz]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Deng]]></surname>
<given-names><![CDATA[X]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia]]></article-title>
<source><![CDATA[J Am Coll Cardiol]]></source>
<year>2016</year>
<volume>67</volume>
<numero>22</numero>
<issue>22</issue>
<page-range>2578-89</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Khera]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Kathiresan]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Genetics of coronary artery disease: discovery, biology and clinical translation]]></article-title>
<source><![CDATA[Nat Rev Genet]]></source>
<year>2017</year>
<volume>18</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>331-44</page-range></nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Benn]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Watts]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Tybjaerg-Hansen]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Nordestgaard]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Familial hypercholesterolemia in the danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication]]></article-title>
<source><![CDATA[J Clin Endocrinol Metab]]></source>
<year>2012</year>
<volume>97</volume>
<numero>11</numero>
<issue>11</issue>
<page-range>3956-64</page-range></nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Miller]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Martin]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Toth]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Santos]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Blaha]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Nasir]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Screening and advanced lipid phenotyping in familial hypercholesterolemia: the Very Large Database of Lipids Study-17 (VLDL-17)]]></article-title>
<source><![CDATA[J Clin Lipidol]]></source>
<year>2015</year>
<volume>9</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>676-83</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sjouke]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Hovingh]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Kastelein]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Stefanutti]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Homozygous autosomal dominant hypercholesterolaemia: prevalence, diagnosis, and current and future treatment perspectives]]></article-title>
<source><![CDATA[Curr Opin Lipidol]]></source>
<year>2015</year>
<volume>26</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>200-9</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Santos]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Bourbon]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Alonso]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Cuevas]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Vasques-Cardenas]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Pereira]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries]]></article-title>
<source><![CDATA[J Clin Lipidol]]></source>
<year>2017</year>
<volume>11</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>160-6</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sturm]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Knowles]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Gidding]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Ahmad]]></surname>
<given-names><![CDATA[Z]]></given-names>
</name>
<name>
<surname><![CDATA[Ahmed]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Ballantyne]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clinical genetic testing for familial hypercholesterolemia: JACC Scientific Expert Panel]]></article-title>
<source><![CDATA[J Am Coll Cardiol]]></source>
<year>2018</year>
<volume>72</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>662-80</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>14</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Futema]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Bourbon]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Williams]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Humphries]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia]]></article-title>
<source><![CDATA[Atherosclerosis]]></source>
<year>2018</year>
<volume>277</volume>
<page-range>457-63</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>15</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Brown]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Goldstein]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[How LDL receptors influence cholesterol and atherosclerosis]]></article-title>
<source><![CDATA[Sci Amer]]></source>
<year>1984</year>
<volume>251</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>58-66</page-range></nlm-citation>
</ref>
<ref id="B16">
<label>16</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hooper]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Burnett]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Bell]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Watts]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The Present and the future of genetic testing in familial hypercholesterolemia: opportunities and caveats]]></article-title>
<source><![CDATA[Curr Atheroscler Rep]]></source>
<year>2018</year>
<volume>20</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>31</page-range></nlm-citation>
</ref>
<ref id="B17">
<label>17</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Alonso]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Díaz-Díaz]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Arrieta]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Fuentes-Jiménez]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[de Andrés]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Saenz]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: insights from SAFEHEART registry]]></article-title>
<source><![CDATA[J Clin Lipidol]]></source>
<year>2016</year>
<volume>10</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>953-61</page-range></nlm-citation>
</ref>
<ref id="B18">
<label>18</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Leigh]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Futema]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Whittall]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Taylor-Beadling]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Williams]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[den Dunnen]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The UCL low-density lipoprotein receptor gene variant database: pathogenicity update]]></article-title>
<source><![CDATA[J Med Genet]]></source>
<year>2017</year>
<volume>54</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>217-23</page-range></nlm-citation>
</ref>
<ref id="B19">
<label>19</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Soria]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Ludwig]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Clarke]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Vega]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Grundy]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[McCarthy]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100]]></article-title>
<source><![CDATA[Proc Natl Acad Sci. U S A]]></source>
<year>1989</year>
<volume>86</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>587-91</page-range></nlm-citation>
</ref>
<ref id="B20">
<label>20</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Andersen]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Miserez]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Ahmad]]></surname>
<given-names><![CDATA[Z]]></given-names>
</name>
<name>
<surname><![CDATA[Andersen]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Familial defective apolipoprotein B-100: a review]]></article-title>
<source><![CDATA[J Clin Lipidol]]></source>
<year>2016</year>
<volume>10</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>1297-302</page-range></nlm-citation>
</ref>
<ref id="B21">
<label>21</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Esperón]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Raggio]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
<name>
<surname><![CDATA[Lorenzo]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Stoll]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mutación en el gen de apolipoproteína B responsable de hipercolesterolemia familiar?: primeros dos casos clínicos reportados en Uruguay]]></article-title>
<source><![CDATA[Rev Urug Cardiol]]></source>
<year>2013</year>
<volume>28</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>182-8</page-range></nlm-citation>
</ref>
<ref id="B22">
<label>22</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Abifadel]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Varret]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Rabès]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Allard]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Ouguerram]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Devillers]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mutations in PCSK9 cause autosomal dominant hypercholesterolemia]]></article-title>
<source><![CDATA[Nat Genet]]></source>
<year>2003</year>
<volume>34</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>154-6</page-range></nlm-citation>
</ref>
<ref id="B23">
<label>23</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Singh]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Gupta]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Collins]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Qamar]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Monda]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Biery]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Familial hypercholesterolemia among young adults with myocardial infarction]]></article-title>
<source><![CDATA[J Am Coll Cardiol]]></source>
<year>2019</year>
<volume>73</volume>
<numero>19</numero>
<issue>19</issue>
<page-range>2439-50</page-range></nlm-citation>
</ref>
<ref id="B24">
<label>24</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Fellin]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Arca]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Zuliani]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Calandra]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Bertolini]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The history of Autosomal Recessive Hypercholesterolemia (ARH). From clinical observations to gene identification]]></article-title>
<source><![CDATA[Gene]]></source>
<year>2015</year>
<volume>555</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>23-32</page-range></nlm-citation>
</ref>
<ref id="B25">
<label>25</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Arca]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Zuliani]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Wilund]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Campagna]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Fellin]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Bertolini]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis]]></article-title>
<source><![CDATA[Lancet]]></source>
<year>2002</year>
<volume>359</volume>
<numero>9309</numero>
<issue>9309</issue>
<page-range>841-7</page-range></nlm-citation>
</ref>
<ref id="B26">
<label>26</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hansel]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Carrié]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Brun-Druc]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Leclert]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Chantepie]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Coiffard]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Premature atherosclerosis is not systematic in phytosterolemic patients: severe hypercholesterolemia as a confounding factor in five subjects]]></article-title>
<source><![CDATA[Atherosclerosis]]></source>
<year>2014</year>
<volume>234</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>162-8</page-range></nlm-citation>
</ref>
<ref id="B27">
<label>27</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Reiner]]></surname>
<given-names><![CDATA[&#381;]]></given-names>
</name>
<name>
<surname><![CDATA[Guardamagna]]></surname>
<given-names><![CDATA[O]]></given-names>
</name>
<name>
<surname><![CDATA[Nair]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Soran]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Hovingh]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Bertolini]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Lysosomal acid lipase deficiency-an under-recognized cause of dyslipidaemia and liver dysfunction]]></article-title>
<source><![CDATA[Atherosclerosis]]></source>
<year>2014</year>
<volume>235</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>21-30</page-range></nlm-citation>
</ref>
<ref id="B28">
<label>28</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Fouchier]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Dallinga-Thie]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Meijers]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Zelcer]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Kastelein]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Defesche]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mutations in STAP1 are associated with autosomal dominant hypercholesterolemia]]></article-title>
<source><![CDATA[Circ Res]]></source>
<year>2014</year>
<volume>115</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>552-5</page-range></nlm-citation>
</ref>
<ref id="B29">
<label>29</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Wintjens]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Bozon]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Belabbas]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[MBou]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Girardet]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Tounian]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France]]></article-title>
<source><![CDATA[J Lipid Res]]></source>
<year>2016</year>
<volume>57</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>482-91</page-range></nlm-citation>
</ref>
<ref id="B30">
<label>30</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Lam]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Singham]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Hegele]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Riazy]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Hiob]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Francis]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Familial hypobetalipoproteinemia-induced nonalcoholic steatohepatitis]]></article-title>
<source><![CDATA[Case Rep Gastroenterol]]></source>
<year>2012</year>
<volume>6</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>429-37</page-range></nlm-citation>
</ref>
<ref id="B31">
<label>31</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Talmud]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Shah]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Whittall]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Futema]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Howard]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Cooper]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study]]></article-title>
<source><![CDATA[Lancet]]></source>
<year>2013</year>
<volume>381</volume>
<numero>9874</numero>
<issue>9874</issue>
<page-range>1293-301</page-range></nlm-citation>
</ref>
<ref id="B32">
<label>32</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Futema]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Shah]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Cooper]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Li]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Whittall]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Sharifi]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries]]></article-title>
<source><![CDATA[Clin Chem]]></source>
<year>2015</year>
<volume>61</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>231-8</page-range></nlm-citation>
</ref>
<ref id="B33">
<label>33</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Do]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Stitziel]]></surname>
<given-names><![CDATA[NO]]></given-names>
</name>
<name>
<surname><![CDATA[Won]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Jørgensen]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Duga]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Angelica Merlini]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction]]></article-title>
<source><![CDATA[Nature]]></source>
<year>2015</year>
<volume>518</volume>
<numero>7537</numero>
<issue>7537</issue>
<page-range>102-6</page-range></nlm-citation>
</ref>
<ref id="B34">
<label>34</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Khera]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Won]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Peloso]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[O&#8217;Dushlaine]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Stitziel]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Association of rare and common variation in the lipoprotein lipase gene with coronary artery disease]]></article-title>
<source><![CDATA[JAMA]]></source>
<year>2017</year>
<volume>317</volume>
<numero>9</numero>
<issue>9</issue>
<page-range>937-46</page-range></nlm-citation>
</ref>
<ref id="B35">
<label>35</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Brown]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Goldstein]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Biomedicine. Lowering LDL: not only how low, but how long?]]></article-title>
<source><![CDATA[Science]]></source>
<year>2006</year>
<volume>311</volume>
<numero>5768</numero>
<issue>5768</issue>
<page-range>1721-3</page-range></nlm-citation>
</ref>
<ref id="B36">
<label>36</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Cohen]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Boerwinkle]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Mosley]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Hobbs]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Sequence variations in PCSK9, low LDL, and protection against coronary heart disease]]></article-title>
<source><![CDATA[N Engl J Med]]></source>
<year>2006</year>
<volume>354</volume>
<numero>12</numero>
<issue>12</issue>
<page-range>1264-72</page-range></nlm-citation>
</ref>
<ref id="B37">
<label>37</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ference]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Majeed]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Penumetcha]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Flack]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Brook]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study]]></article-title>
<source><![CDATA[J Am Coll Cardiol]]></source>
<year>2015</year>
<volume>65</volume>
<numero>15</numero>
<issue>15</issue>
<page-range>1552-61</page-range></nlm-citation>
</ref>
<ref id="B38">
<label>38</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Teslovich]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Musunuru]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Smith]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Edmondson]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Stylianou]]></surname>
<given-names><![CDATA[I]]></given-names>
</name>
<name>
<surname><![CDATA[Koseki]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Biological, clinical and population relevance of 95 loci for blood lipids]]></article-title>
<source><![CDATA[Nature]]></source>
<year>2010</year>
<volume>466</volume>
<numero>7307</numero>
<issue>7307</issue>
<page-range>707-13</page-range></nlm-citation>
</ref>
<ref id="B39">
<label>39</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Mata]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Alonso]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Pérez Jiménez]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Detección de la hipercolesterolemia familiar: un modelo de medicina preventiva]]></article-title>
<source><![CDATA[Rev Esp Cardiol]]></source>
<year>2014</year>
<volume>67</volume>
<numero>9</numero>
<issue>9</issue>
<page-range>685-8</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
