Clinical report
Pulmonary arterial hypertension and portal hypertension in a patient with hereditary hemorrhagic telangiectasia
Hipertensión arterial pulmonar e hipertensión portal en un paciente con telangiectasia hemorrágica hereditaria
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Bottom: After encountering paternal-derived antigens in the periphery or in the genital tract, antigen-specific Tregs are generated. This specific Treg population could expand later, as paternal–foetal alloantigens are continuously released to the periphery. Tregs would then migrate into foetal–maternal interface where they would help to create a site of immune privilege characterized by high levels of protective molecules, e.g. HO-1, LIF, IDO, TGFβ, IL-10 and PIBF. Furthermore, Tregs maintain adequate NK3/NK1 cell subpopulation preventing trophoblast injury and permit a sufficient angiogenesis. In the end, Tregs may down-regulate maternal allo-response to foetal–paternal antigens, preventing apoptosis of trophoblast cells.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jaume Alijotas-Reig, Taisiia Melnychuk, Josep Maria Gris" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Jaume" "apellidos" => "Alijotas-Reig" ] 1 => array:2 [ "nombre" => "Taisiia" "apellidos" => "Melnychuk" ] 2 => array:2 [ "nombre" => "Josep Maria" "apellidos" => "Gris" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775314001341?idApp=UINPBA00004N" "url" => "/00257753/0000014400000006/v2_201502230228/S0025775314001341/v2_201502230228/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S002577531400760X" "issn" => "00257753" "doi" => "10.1016/j.medcli.2014.10.007" "estado" => "S300" "fechaPublicacion" => "2015-03-15" "aid" => "3147" "copyright" => "Elsevier España, S.L.U." 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Reality or a selection bias?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Vicente Navarro López" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Vicente" "apellidos" => "Navarro López" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020615001515" "doi" => "10.1016/j.medcle.2014.10.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020615001515?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531400760X?idApp=UINPBA00004N" "url" => "/00257753/0000014400000006/v2_201502230228/S002577531400760X/v2_201502230228/es/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Clinical report</span>" "titulo" => "Pulmonary arterial hypertension and portal hypertension in a patient with hereditary hemorrhagic telangiectasia" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "261" "paginaFinal" => "264" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Guillermo Pousada, Adolfo Baloira, Diana Valverde" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Guillermo" "apellidos" => "Pousada" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "Adolfo" "apellidos" => "Baloira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:4 [ "nombre" => "Diana" "apellidos" => "Valverde" "email" => array:1 [ 0 => "dianaval@uvigo.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, Vigo, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Biomedical Research Institute of Vigo (IBIV), Vigo, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Respiratory Division, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipertensión arterial pulmonar e hipertensión portal en un paciente con telangiectasia hemorrágica hereditaria" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2626 "Ancho" => 3479 "Tamanyo" => 652969 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Electropherograms showing the pathogenic mutations identified in <span class="elsevierStyleItalic">BMPR2</span>, <span class="elsevierStyleItalic">ACVRL1</span>, <span class="elsevierStyleItalic">ENG</span> and <span class="elsevierStyleItalic">TRPC6</span> genes in the analyzed patient.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary arterial hypertension (PAH) is a rare disease with a complex pathogenesis that may be heritable, idiopathic or associated with other diseases, drugs or toxics and possibly influenced by genetic factors. Group I of the Nice classification includes idiopathic and hereditary forms and others associated to connective tissue diseases, portal hypertension, HIV infection, schistosomiasis and congenital heart diseases.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> More than 70% of the hereditary cases are carriers of mutations in the gene that codifies for the Bone morphogenetic protein receptor type 2 (<span class="elsevierStyleItalic">BMPR2</span>). Although familial individuals of a PAH patient with a <span class="elsevierStyleItalic">BMPR2</span> mutation and carrying the mutation have a risk to develop the disease of around 20%, indicating that more than a single mutation is necessary to develop PAH, perhaps other genetic or exogenous factors play a role.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with a prevalence of approximately 10 cases per 100,000 inhabitants. HHT is characterized by the presence of epistaxis, mucocutaneous telangiectasias and lung, brain and liver vascular malformations. PAH is a rare complication of HHT, which happens in less than 1% of the cases but implies a marked worsening of prognosis. The genes of Activin receptor like kinase 1 (<span class="elsevierStyleItalic">ACVRL1</span>) and Endoglin (<span class="elsevierStyleItalic">ENG</span>) seem to have an important role in its pathogenesis.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Liver cirrhosis with portal hypertension is also associated with the presence of PAH in 1–2% of cases <a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>. We present a patient with HHT and liver cirrhosis with portal hypertension that developed PAH. Likely, the interaction between all of these factors favors the appearance of PAH.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 62-year-old male was sent to our Unit of PAH because of dyspnea on exertion and suspicion of PAH in an echocardiographic study. He was diagnosed 25 years before of HHT with spontaneous and very frequent nose bleeds, chronic iron deficiency anemia and multiple cutaneous and digestive telangiectasias, including esophagus, stomach and colon, with several episodes of gastrointestinal bleeding. He had no known family history of the disease and only a healthy daughter. In 1981, a secundum atrial septal defect was corrected with no later problems and there were several normal echocardiograms in subsequent reviews. He was a heavy alcohol drinker, and four years before he was detected to have alcohol liver cirrhosis with a single episode of bleeding from one esophageal vein in 2009. In late 2010, a CT (computer tomography) scan showed the presence of portal hypertension without ascites. At that time he was in functional class (FC) I. A year later he began to notice dyspnea on ordinary exertion and subsequently orthopnea and dizziness. He was referred to our Unit 6 months after onset of symptoms, with an echocardiogram that showed marked dilatation of the right cavities, severe tricuspid regurgitation, TAPSE 18<span class="elsevierStyleHsp" style=""></span>mm and an estimated pulmonary systolic pressure of 80<span class="elsevierStyleHsp" style=""></span>mmHg. At this time he was in FC III, with Child–Pugh score B7. On physical examination BP was 115/55<span class="elsevierStyleHsp" style=""></span>mmHg, pulse was 89 beats/min and respiratory rate 17 breaths/min. Pulmonary function tests were normal, and a 6-min walk distance was 275<span class="elsevierStyleHsp" style=""></span>m, with a resting oxygen saturation on room air of 93% and 74% at the end of the test. The plasma concentration of BNP was 267<span class="elsevierStyleHsp" style=""></span>pg/ml. A pulmonary V/Q scanning was normal. The CT scan showed large dilated main pulmonary arteries with a diameter of nearly 3<span class="elsevierStyleHsp" style=""></span>cm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), but no pulmonary vascular malformations. The liver was large with increasing diameter of the hepatic veins and minimal ascites. Cardiac catheterization was performed showing a mean pulmonary arterial pressure of 60<span class="elsevierStyleHsp" style=""></span>mmHg, systolic pulmonary arterial pressure of 85<span class="elsevierStyleHsp" style=""></span>mmHg, pulmonary capillary wedge pressure of 14<span class="elsevierStyleHsp" style=""></span>mmHg, mean right atrial pressure of 12<span class="elsevierStyleHsp" style=""></span>mmHg, cardiac output of 4.9<span class="elsevierStyleHsp" style=""></span>L/min, and pulmonary vascular resistance of 871<span class="elsevierStyleHsp" style=""></span>d/s/cm<span class="elsevierStyleSup">−5</span>. The left cavities were normal with not passage of contrast to the right. The vasodilator test with epoprostenol was negative. The patient was treated with ambrisentan 5<span class="elsevierStyleHsp" style=""></span>mg/d with mild clinical improvement for 2 months but worsened again and the dose was increased to 10<span class="elsevierStyleHsp" style=""></span>mg/d and tadalafil 40<span class="elsevierStyleHsp" style=""></span>mg/d. was added After two weeks of treatment without improvement, subcutaneous teprostinil was added but the patient had epistaxis and recurrent lower gastrointestinal bleeding in relation to multiple telangiectasias in the colon that drove frequent blood transfusions. He developed severe anemia, progressive renal failure, hyponatremia, generalized edema and finally died three weeks later.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">After informed consent, we conducted a genetic study that included <span class="elsevierStyleItalic">BMPR2</span>, <span class="elsevierStyleItalic">ACVRL1</span>, <span class="elsevierStyleItalic">ENG</span> and <span class="elsevierStyleItalic">KCNA5</span> (voltage-gated potassium channel) genes. PolyPhen, Sift and pMUT informatics programs were used to evaluate the potential pathogenicity in the case of missense mutations and NNSplice and NetGene to test their possible involvement in splicing. In <span class="elsevierStyleItalic">BMPR2</span> gene we found a potentially pathogenic missense mutation, c.1021G>A (V341L), and one synonymous mutation, c.327G>A (p.Q109Q), which could affect splicing. In <span class="elsevierStyleItalic">ACVRL1</span> two changes were presents in the intronic region, c.313+20C>A, which seems to have no effect, and c.1502+7A>G which could also affect the splicing. The <span class="elsevierStyleItalic">ENG</span> gene showed a single mutation in exon 4, c.498G>A (Q166Q) with possible involvement in the splicing. No pathogenic mutations were found for <span class="elsevierStyleItalic">KCNA5</span> gene. The patient also had single nucleotide polymorphisms in the gene, for the Canonical transient receptor potential channels of calcium 6 (<span class="elsevierStyleItalic">TRPC6</span>), c.1-361A>T, c.1-254C>G and c.1-218C>T, which appears to increase the likelihood of developing PAH. The mutations can be show in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">This case illustrates the complexity of the pathogenesis of PAH. Although there are other diseases, toxic, drugs or genetic alterations associated with this disease, none by itself seems to be sufficient to develop it. HHT is a relatively common disease, but the presence of PAH occurs in no more than 1% of all patients. Portal hypertension also has a high prevalence but the risk of clinically relevant PAH is probably less than 2%. <span class="elsevierStyleItalic">BMPR2</span> mutations, the most important genetic alteration associated with PAH, lead to occurrence of disease in only 1 out of 5 carriers, possibly indicating that in most of cases it requires the presence of a second hit. Numerous mechanisms are involved in regulation of pulmonary vascular tone and in maintaining a proper endothelial function. It is likely that a pathological change in only one of them can be compensated at least in part and does not have significant consequences, but the coexistence of several damaged cell signals or the occurrence of an external agent may exceed the compensation mechanisms. It has been reported the case of a woman with HHT and gross deletion of <span class="elsevierStyleItalic">ENG</span> gene who developed PAH after years of methamphetamine consumption.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Our patient had two PAH-associated diseases and was carrying several mutations in <span class="elsevierStyleItalic">BMPR2</span>, <span class="elsevierStyleItalic">ACVRL1</span> and <span class="elsevierStyleItalic">ENG</span>, some of them with potential pathogenic effect. Mutations in <span class="elsevierStyleItalic">ACVRL1</span> usually are associated with an early onset of PAH, often teenagers or children, with an average of 22 years.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In our case, the age of onset was clearly superior, but it should be noted that our patient had a mutation whose effects are only likely pathogenic. He was also carrying another potential pathogenic mutation in <span class="elsevierStyleItalic">ENG</span> gene, although this gene appears to be less important in the development of PAH. Furthermore, he showed three single nucleotide polymorphisms in <span class="elsevierStyleItalic">TRPC6</span> gene that increases expression of this receptor leading to an increase of the cellular influx of Ca<span class="elsevierStyleSup">2+</span> into the muscle cells of pulmonary arteries in patients with PAH.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This polymorphism is almost three times more frequent in these patients than in healthy population. The genetic basis of the PAH has been expanding in recent years. An association between some single-nucleotide polymorphisms of <span class="elsevierStyleItalic">KCNA5</span> and PAH related to scleroderma have been described.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">It is difficult to know to what extent each of the diseases contributed to the development of PAH. There are significant gaps in our knowledge of the molecular mechanisms underlying the disease but we know that the various pathways involved in the pathogenesis of PAH have important relations between them, for example, <span class="elsevierStyleItalic">BMPR2</span> and <span class="elsevierStyleItalic">ENG</span>,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> a key player in PAH, or Nitric oxide.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Liver cirrhosis was of moderate severity in our case, but there is no clear relationship between severity of portal hypertension and PAH. A case-control study found a significant association with female sex and liver autoimmune diseases,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> none of which occurred in our case. However, the fact of the appearance of PAH at a relatively late age, a few years after the diagnosis of portal hypertension and a relatively high cardiac output suggests an important role of liver disease. The presence of HHT associated with some mutations with possible pathogenic potential is another major risk factor in our patient in whom added genetic variants may also favor the development of PAH. Those patients with increased risk of developing PAH should be studied for the presence of genetic variants since the risk could increase significantly.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The poor prognosis, strongly influenced by PAH, was also marked by intractable bleeding due to HHT.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, we present a case with PAH in which diverse circumstances may play a role favoring the disease, including genetics. A greater understanding of the genes involved in the development of PAH will help us to better define susceptible individuals, and thereby facilitate advice on avoiding substances or situations that increase the risk of PAH or follow more closely patients with associated diseases.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">A. Baloira has participated as a consultant for Actelion, GSK, Ferrer and Pfizer and has received research grants from Actelion.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres436899" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec460110" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres436900" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec460109" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-04-22" "fechaAceptado" => "2014-09-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec460110" "palabras" => array:4 [ 0 => "Pulmonary arterial hypertension" 1 => "Hereditary hemorrhagic telangiectasia" 2 => "Portal hypertension" 3 => "Mutations" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec460109" "palabras" => array:4 [ 0 => "Hipertensión arterial pulmonar" 1 => "Telangiectasia hemorrágica hereditaria" 2 => "Hipertensión portal" 3 => "Mutaciones" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pulmonary arterial hypertension (PAH) is a rare disease that could be inherited with an autosomal dominant pattern. Mutations in <span class="elsevierStyleItalic">BMPR2</span> gene are described in over 70% of cases, although other genes are involved in lesser extend in PAH. Hereditary hemorrhagic telangiectasia (HHT) is another rare autosomal dominant disease. PAH is a rare complication of HHT that occurs in less than 1% of cases. Liver cirrhosis with portal hypertension is also associated with the presence of PAHs in 1–2% of cases.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We present here a patient with HHT who developed PAH shortly after showing portal hypertension.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Some genes (<span class="elsevierStyleItalic">BMPR2</span>, <span class="elsevierStyleItalic">ACVRL1</span>, <span class="elsevierStyleItalic">ENG</span>) seem to play an important role in PAH pathogenesis. We analyzed these genes, detecting mutations in <span class="elsevierStyleItalic">BMPR2</span> gene (c.1021G>A (V341L), c.327G>A (p.Q109Q)), <span class="elsevierStyleItalic">ACVRL1</span> (c.313+20C>A, c.1502+7A>G) and <span class="elsevierStyleItalic">ENG</span> (c.498G>A (Q166Q)). The patient also had 3 polymorphisms in the <span class="elsevierStyleItalic">TRPC6</span> gene (c.1-361A>T, c.1-254C>G, c.1-218C>T).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The study of these genes will help us to identify and track individuals susceptible for developing PAH associated with other diseases.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La hipertensión arterial pulmonar (HAP) es una enfermedad rara que en la forma hereditaria se expresa como una afección autosómica dominante. Las mutaciones en el gen <span class="elsevierStyleItalic">BMPR2</span> son características en más del 70% de los casos, y otros genes están envueltos en la compleja patogénesis de la HAP. La telangiectasia hemorrágica hereditaria (THH) es otra enfermedad rara autosómica dominante. La HAP es una complicación rara de la THH que ocurre en menos del 1% de los casos. La cirrosis hepática con hipertensión portal también se asocia con la presencia de HAP en el 1–2% de los casos.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Presentamos un paciente con THH que desarrolló HAP poco tiempo después de presentar hipertensión portal.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Varios genes (<span class="elsevierStyleItalic">BMPR2</span>, <span class="elsevierStyleItalic">ACVRL1</span>, <span class="elsevierStyleItalic">ENG</span>) parecen tener un papel importante en su patogénesis. Se estudiaron a nivel molecular los cambios en estos genes, encontrándose mutaciones en el gen <span class="elsevierStyleItalic">BMPR2</span> (c.1021G>A (V341L), c.327G>A (p.Q109Q)), <span class="elsevierStyleItalic">ACVRL1</span> (c.313+20C>A, c.1502+7A>G) y <span class="elsevierStyleItalic">ENG</span> (c.498G>A (Q166Q))<span class="elsevierStyleItalic">.</span> El paciente también presenta 3 polimorfismos en el gen <span class="elsevierStyleItalic">TRPC6</span> (c.1-361A>T, c.1-254C>G, c.1-218C>T).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El estudio de estos genes nos ayudará a definir y seguir los individuos susceptibles de desarrollar HAP asociada a otras enfermedades.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1044 "Ancho" => 1625 "Tamanyo" => 193115 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">In this CT, an increase in the diameter of the pulmonary arteries without vascular malformationsis observed.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2626 "Ancho" => 3479 "Tamanyo" => 652969 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Electropherograms showing the pathogenic mutations identified in <span class="elsevierStyleItalic">BMPR2</span>, <span class="elsevierStyleItalic">ACVRL1</span>, <span class="elsevierStyleItalic">ENG</span> and <span class="elsevierStyleItalic">TRPC6</span> genes in the analyzed patient.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Updated clinical classification of pulmonary arterial hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. 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