A novel JAG1 mutation causing Alagille syndrome presenting with giant hepatic nodules and discordant phenotype in monozygotic twins

Zhang, Yi; Xiang, Bo; Yu, Xijie

doi:10.1016/j.medcli.2019.06.009

array:24 ["pii" => "S0025775319304919" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.06.009" "estado" => "S300" "fechaPublicacion" => "2020-12-11" "aid" => "4938" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2019" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2020;155:507-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S2387020620305301" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.06.044" "estado" => "S300" "fechaPublicacion" => "2020-12-11" "aid" => "4938" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2020;155:507-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Scientific letter" "titulo" => "A novel JAG1 mutation causing Alagille syndrome presenting with giant hepatic nodules and discordant phenotype in monozygotic twins" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "507" "paginaFinal" => "509" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1887 "Ancho" => 2917 "Tamanyo" => 539618 ] ] "descripcion" => array:1 [ "en" => "Clinical features and genetic results in the family of monozygotic twins. (a) Facial dysmorphism of twins and the mother. (b) Posterior embryotoxon (black arrow) in eyes of Ttwin A and Twin B, the mother had normal eyes. (c) A similar giant liver lesion is present in twins. (d) Butterfly vertebra (white arrow) in T8 of Twin A. (e) Single kidney of Twin A. (f) Chromatogram showing genetic mutation (c.2801_c.2802delGCinsT; p. G934Vfs*11)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Yi Zhang, Bo Xiang, Xijie Yu" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Yi" "apellidos" => "Zhang" ] 1 => array:2 [ "nombre" => "Bo" "apellidos" => "Xiang" ] 2 => array:2 [ "nombre" => "Xijie" "apellidos" => "Yu" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0025775319304919" "doi" => "10.1016/j.medcli.2019.06.009" "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/S0025775319304919?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620305301?idApp=UINPBA00004N" "url" => "/23870206/0000015500000011/v1_202012152105/S2387020620305301/v1_202012152105/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S0025775319305251" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.07.012" "estado" => "S300" "fechaPublicacion" => "2020-12-11" "aid" => "4971" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2020;155:509-10" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2 "PDF" => 2 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "Carta científica" "titulo" => "Capilaroscopia periungueal en el Grupo Español de Enfermedades Autoinmunes Sistémicas (GEAS). Resultados de una encuesta electrónica" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "509" "paginaFinal" => "510" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Nailfold capillaroscopy in the Spanish Group of Systemic Autoimmune Diseases (GEAS). Results of an electronic survey" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:2 [ 0 => array:2 [ "autoresLista" => "Luis Sáez-Comet, Patricia Fanlo-Mateo, Borja Gracia-Tello" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Luis" "apellidos" => "Sáez-Comet" ] 1 => array:2 [ "nombre" => "Patricia" "apellidos" => "Fanlo-Mateo" ] 2 => array:2 [ "nombre" => "Borja" "apellidos" => "Gracia-Tello" ] 3 => array:1 [ "colaborador" => "en representación del GREC (Grupo Español de Capilaroscopias)" ] ] ] 1 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "Otros miembros del Grupo Español de Capilaroscopias" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020620305222" "doi" => "10.1016/j.medcle.2019.07.027" "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/S2387020620305222?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319305251?idApp=UINPBA00004N" "url" => "/00257753/0000015500000011/v1_202012080624/S0025775319305251/v1_202012080624/es/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0025775319304865" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.05.032" "estado" => "S300" "fechaPublicacion" => "2020-12-11" "aid" => "4933" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2020;155:506-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "Carta científica" "titulo" => "Prevalencia de uveítis en una población española, estudio UveCAM" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "506" "paginaFinal" => "507" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Prevalence of uveitis in a Spanish population, UveCAM study" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:2 [ 0 => array:2 [ "autoresLista" => "Ángel M. García-Aparicio, Laura Alonso Martín, Ricardo Quirós Zamorano" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Ángel M." "apellidos" => "García-Aparicio" ] 1 => array:2 [ "nombre" => "Laura" "apellidos" => "Alonso Martín" ] 2 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Quirós Zamorano" ] ] ] 1 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "Resto de miembros del Grupo del Estudio UveCAM" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020620305155" "doi" => "10.1016/j.medcle.2019.05.041" "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/S2387020620305155?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319304865?idApp=UINPBA00004N" "url" => "/00257753/0000015500000011/v1_202012080624/S0025775319304865/v1_202012080624/es/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "Scientific letter" "titulo" => "A novel JAG1 mutation causing Alagille syndrome presenting with giant hepatic nodules and discordant phenotype in monozygotic twins" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "507" "paginaFinal" => "509" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Yi Zhang, Bo Xiang, Xijie Yu" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Yi" "apellidos" => "Zhang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Bo" "apellidos" => "Xiang" "email" => array:1 [ 0 => "xb_scu.edu@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "Xijie" "apellidos" => "Yu" "email" => array:2 [ 0 => "xijieyu@hotmail.com" 1 => "xijieyu@scu.edu.cn" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Laboratory of Endocrinology and Metabolism, Department of Endocrinology and Metabolism, and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1887 "Ancho" => 2917 "Tamanyo" => 539618 ] ] "descripcion" => array:1 [ "en" => "Clinical features and genetic results in the family of monozygotic twins. (a) Facial dysmorphism of twins and the mother. (b) Posterior embryotoxon (black arrow) in eyes of Ttwin A and Twin B, the mother had normal eyes. (c) A similar giant liver lesion is present in twins. (d) Butterfly vertebra (white arrow) in T8 of Twin A. (e) Single kidney of Twin A. (f) Chromatogram showing genetic mutation (c.2801_c.2802delGCinsT; p. G934Vfs*11)." ] ] ] "textoCompleto" => "Alagille syndrome (ALGS) is a rare autosomal dominant genetic disorder with multisystem organ involvement. Pathogenic variants in the genes encoding Jagged1 (JAG1) and Notch 2 (NOTCH2) in the Notch signaling pathway have been identifiedOda, Elkahloun, Pike, Okajima, Krantz, Genin, Piccoli, Meltzer, Spinner, Collins, Chandrasekharappa.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> The clinical diagnosis can be made in the presence of bile duct paucity, along with 3 or more of the following major features: chronic cholestasis, cardiac defects, skeletal abnormalities, ocular abnormalities and characteristic facies. Nevertheless, the widely variable phenotype in ALGS raises questions about the primary role of the genotype in giving rise to features, or whether at least some of the effects are secondary to nongenetic factors.This was a pair of monochorionic female twins born after 34 weeks of gestation. The family history was unremarkable, and there was no history of consanguinity. Twin A presented with intermittent pruritus and stomachache at 10 years old. Twin B had similar but less prominent symptoms. Twin A weighed 23.5kg (−1.93SD) and height was 129.5cm (−2.15SD). Pertinent physical findings included pointed chin, deep set eyes, short nose, triangular face, broad forehead. Laboratory tests revealed elevated liver function test markers. Computed tomography showed butterfly vertebrae of T8, lack of left kidney, an 8.5×6.5×9.5cm lesion located in the right trisegment of the liver. A hepatic biopsy showed absence of bile duct. Ophthalmologic examination showed posterior embryotoxon in the right eye. An echocardiogram was normal.The weight of Twin B was 23kg (−2.08SD) and her height was 129cm (−2.23SD). She had the same characteristic face as Twin A. Impairment in her liver function was detected. Computed tomography showed a 8.1×9.0×7.7cm lesion located in the right trisegment of the liver. No vertebral and renal abnormalities were detected. Ophthalmologic examination revealed posterior embryotoxon in the left eye. Cardiac ultrasonography revealed a thickening of the coronary sinus of approximately 11cm. The clinical information of the twins and the mother is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The genetic testing revealed a heterozygous variant in the JAG1 gene, p.G934Vfs*11 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The frameshift mutation in the 23rd exon of JAG1 (c.2801_c.2802delGCinsT; p. G934Vfs*11) in both twins was inherited from their mother, while the JAG1 gene in their father was wild type.To our knowledge, this is the third observation of monozygotic twins with ALGS. Due to the widely variant phenotype of ALGS, it is quite confused about which factors contributing to the developmental defects of organs. Since monozygotic twins are believed to have identical genetic information, we could find some clues combining the three cases of monozygotic twins with ALGS.<a class="elsevierStyleCrossRefs" href="#bib0035">2,3</a>Chronic cholestasis occurs in a very high proportion (∼95%) of cases, and most commonly, presents in the neonatal period or first 3 months of life, with jaundice due to conjugated hyperbilirubinemia. In the three pairs of monozygotic twins, all of them had liver involvement but with different severity. Notch signaling is tightly linked with the development of bile ducts. Izumi et al. proposed the fetal hypoxia may modify the liver disease severity of ALGS in monozygotic twins.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Animal studies revealed that the Fringe genes including Lunatic (Lfng), Radical (Rfng), and Manic (Mfng) may regulate postnatal bile duct growth and remodeling.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> Hence, JAG1 mutations largely cause the liver phenotype of ALGS, while environmental factors and genetic modifiers may affect the phenotypic severity.More than 90% ALGS patients have cardiovascular anomalies and characteristic facies. Three pairs of twins had facial features and five patients had cardiac defects, highlighting roles of Jag1 in the heart development. The cause of the facies has been debatable. It has been proposed that the facial dysmorphism is secondary to congenital intrahepatic cholestasis while Kamath et al. implied it was specific but not a common endpoint of cholestasis.<a class="elsevierStyleCrossRef" href="#bib0050">5</a> Interestingly, renal anomalies occurred in almost half of twins. The role of NOTCH2 and JAG1 in formation of proximal tubules and podocytes might explain the renal dysplasia and proteinuria. Further researches are needed on how specific human mutations lead to kidney defects.It is a very complex process how JAG1 mutations lead to multisystem defects through the Notch signaling pathway, also environmental factors and genetic modifiers should be considered. Further efforts into understanding the transcriptional control of Notch genes will be essential for deciphering how variable mutations affect gene regulation and impact on disease." "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1887 "Ancho" => 2917 "Tamanyo" => 539618 ] ] "descripcion" => array:1 [ "en" => "Clinical features and genetic results in the family of monozygotic twins. (a) Facial dysmorphism of twins and the mother. (b) Posterior embryotoxon (black arrow) in eyes of Ttwin A and Twin B, the mother had normal eyes. (c) A similar giant liver lesion is present in twins. (d) Butterfly vertebra (white arrow) in T8 of Twin A. (e) Single kidney of Twin A. (f) Chromatogram showing genetic mutation (c.2801_c.2802delGCinsT; p. G934Vfs*11)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the human Jagged1 gene are responsible for Alagille syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Oda" 1 => "A.G. Elkahloun" 2 => "B.L. Pike" 3 => "K. Okajima" 4 => "I.D. Krantz" 5 => "A. Genin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Nat Genet" "fecha" => "1997" "volumen" => "16" "paginaInicial" => "235" "paginaFinal" => "242" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monozygotic twins with a severe form of Alagille syndrome and phenotypic discordance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B.M. Kamath" 1 => "I.D. Krantz" 2 => "N.B. Spinner" 3 => "J.E. Heubi" 4 => "D.A. Piccoli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.10610" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2002" "volumen" => "112" "paginaInicial" => "194" "paginaFinal" => "197" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12244555" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discordant clinical phenotype in monozygotic twins with Alagille syndrome: possible influence of non-genetic factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Izumi" 1 => "D. Hayashi" 2 => "C.M. Grochowski" 3 => "N. Kubota" 4 => "E. Nishi" 5 => "M. Arakawa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Med Genet A" "fecha" => "2016" "volumen" => "170" "paginaInicial" => "471" "paginaFinal" => "475" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bile duct proliferation in Jag1/fringe heterozygous mice identifies candidate modifiers of the Alagille syndrome hepatic phenotype" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Ryan" 1 => "C. Bales" 2 => "A. Nelson" 3 => "D.M. Gonzalez" 4 => "L. Underkoffler" 5 => "M. Segalov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.22538" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2008" "volumen" => "48" "paginaInicial" => "1989" "paginaFinal" => "1997" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19026002" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Facial features in Alagille syndrome: specific or cholestasis facies?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.M. Kamath" 1 => "K.M. Loomes" 2 => "R.J. Oakey" 3 => "K.E. Emerick" 4 => "T. Conversano" 5 => "N.B. Spinner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.10579" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2002" "volumen" => "112" "paginaInicial" => "163" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12244550" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack498835" "titulo" => "Acknowledgements" "texto" => "The authors appreciate the efforts of Dr. Kewei Li for assistance of the case. This work was supported by grants from the National Natural Science Foundation of China (Nos. 81770875, 81572639), the Science and Technology Department of Sichuan Province (2018SZ0142), and Sichuan University (2018SCUH0093)." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/00257753/0000015500000011/v1_202012080624/S0025775319304919/v1_202012080624/en/main.assets" "Apartado" => array:4 [ "identificador" => "66447" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00257753/0000015500000011/v1_202012080624/S0025775319304919/v1_202012080624/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319304919?idApp=UINPBA00004N"]

ISSN: 0025-7753

Medicina Clínica, fundada en 1943, es la única publicación semanal de contenido clínico que se edita en España y constituye el máximo exponente de la calidad y pujanza de la medicina española. Son características fundamentales de esta publicación el rigor científico y metodológico de sus artículos, la actualidad de los temas y, sobre todo, su sentido práctico, buscando siempre que la información sea de la mayor utilidad en la práctica clínica. Los contenidos de Medicina Clínica abarcan dos frentes: trabajos de investigación original rigurosamente seleccionados atendiendo a su calidad, originalidad e interés, y trabajos orientados a la formación continuada, encomendados por la revista a autores relevantes (Editoriales, Revisiones, Conferencias clínicas y clínico-patológicas, Diagnóstico y Tratamiento). En estos artículos se ponen al día aspectos de destacado interés clínico o conceptual en la medicina actual. Medicina Clínica es un vehículo de información científica de reconocida calidad, como demuestra su inclusión en los más prestigiosos y selectivos índices bibliográficos del mundo.

Ver más Opción Open Access

Indexada en:

Current Contents/Clinical Medicine, Journal Citation Reports, SCI-Expanded, Index Medicus/Medline, Excerpta Medica/EMBASE, IBECS, IME, MEDES, PASCAL, SCOPUS, ScienceDirect