Case and Research Letter
Skin Lesions Associated With a New Mutation in the RECQL4 Gene in a Patient With Osteosarcoma
Lesiones cutáneas en una paciente con osteosarcoma asociadas a una nueva mutación en el gen RECQL4
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Ortiz-de Frutos" "autores" => array:3 [ 0 => array:4 [ "nombre" => "F." "apellidos" => "Tous-Romero" "email" => array:1 [ 0 => "Fatimatousro@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "Palma-Milla" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Ortiz-de Frutos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Genética, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lesiones cutáneas en una paciente con osteosarcoma asociadas a una nueva mutación en el gen RECQL4" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 480 "Ancho" => 755 "Tamanyo" => 61331 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Poikiloderma-like lesions, with areas of atrophic skin and lentiginous pigmentary abnormalities on the arms.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 35-year-old woman from Ecuador whose history was remarkable for osteosarcoma in infancy (currently in remission) came to our department for assessment of progressive growth of a lesion on her right leg. The lesion had been present for at least 5 years. The patient also reported having had verrucous lesions on her hands and feet since adolescence (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The examination revealed poikiloderma-type skin in sun-exposed areas (face, neck, and limbs), with areas of atrophic skin, depigmentation, and lentiginous pigmentation (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>). She reported having had these skin problems since birth. The lesion on the right leg was removed. Histopathology confirmed a diagnosis of Bowen disease. Given her history of osteosarcoma during infancy, poikiloderma-type skin abnormalities, verrucous lesions, and skin cancer at such an early age, we made a presumptive diagnosis of Rothmund-Thomson syndrome (RTS). This diagnosis was confirmed by a genetic study, which revealed a homozygous variant in the <span class="elsevierStyleItalic">RECQL4</span> gene, namely, c.3236G>T (p.S1079I). This mutation had not been previously reported in the literature, although the change that occurred (sense change in the last nucleotide of exon 19 of the <span class="elsevierStyleItalic">RECQL4</span> gene) makes it very likely that this was a pathogenic mutation. Furthermore, the Human Gene Mutation Database contains missense variants in adjacent regions associated with RTS. It was not possible to perform a genetic analysis of the patient's parents (nonconsanguineous), since they lived in Ecuador.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">RTS (OMIM#<a href="omim:268400">268400</a>) is a rare autosomal recessive genetic skin disease characterized by erythematous plaques and patches (occasionally edematous and bullous lesions) that appear during childhood on sun-exposed areas, mainly on the cheeks and limbs. Over the years, the lesions atrophy, with telangiectasia and areas of lentiginous depigmentation and pigmentation. Other findings include short stature, hair loss (scalp, eyebrows, and eyelashes), skeletal abnormalities, juvenile cataracts, hypogonadism, gastrointestinal disorders, and susceptibility to malignant diseases (mainly osteosarcoma and skin cancer).<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Two types of RTS have been reported. Type I disease (35–40% of cases) is characterized by poikiloderma, ectodermal dysplasia, and juvenile cataracts. Type II disease (60–65%), on the other hand, is characterized by the additional presence of poikiloderma, congenital bone defects, and an increased risk of osteosarcoma (reported in 30% of patients with RTS).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Type II RTS is associated with heterozygous or homozygous mutations in the DNA helicase gene <span class="elsevierStyleItalic">RECQL4</span>.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> Some 400 cases of RTS have been reported to date.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We highlight the importance of suspecting RTS in children with poikiloderma-like abnormalities. This approach will facilitate the early diagnosis of other, potentially severe associations, such as malignant disease. In middle-aged persons, as in the case we report, a history of osteosarcoma, together with the presence of skin abnormalities, should alert us to the possibility of RTS.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1289 "Ancho" => 755 "Tamanyo" => 235384 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Verrucous lesions on the hands.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 560 "Ancho" => 755 "Tamanyo" => 63858 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Poikiloderma-like lesions, with areas of atrophic skin on the posterior aspect of the neck.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 480 "Ancho" => 755 "Tamanyo" => 61331 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Poikiloderma-like lesions, with areas of atrophic skin and lentiginous pigmentary abnormalities on the arms.</p>" ] ] ] "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" => "Rothmund-Thomson syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. 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Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JAAD Case Rep" "fecha" => "2017" "volumen" => "3" "paginaInicial" => "172" "paginaFinal" => "174" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.L. Wang" 1 => "A. Gannavarapu" 2 => "C.A. Kozinetz" 3 => "M.L. Levy" 4 => "R.A. Lewis" 5 => "M.M. Chintagumpala" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jnci/95.9.669" "Revista" => array:6 [ "tituloSerie" => "J Natl Cancer Inst" "fecha" => "2003" "volumen" => "95" "paginaInicial" => "669" "paginaFinal" => "674" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12734318" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000011300000010/v1_202211300529/S0001731022008213/v1_202211300529/en/main.assets" "Apartado" => array:4 [ "identificador" => "6143" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas científico-clínicas" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00017310/0000011300000010/v1_202211300529/S0001731022008213/v1_202211300529/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731022008213?idApp=UINPBA000044" ]
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