Case Letter
Rare presentation of Rothmund-Thomson syndrome with novel compound heterozygous mutations of the RECQL4 gene
Department of Dermatology, Second Affiliated Hospital, Xi’An Jiaotong University, Shaanxi, China
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Uma estava no local do <span class="elsevierStyleItalic">splicing</span>, c.1391‐2A> C, proveniente do pai e também observada na irmã. 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One was in the splice site, c.1391-2A>C from her father, and also was seen in her sister. The other was a deletion mutation, c.2492_2493delAT (p.His831Argfs) from her mother.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder that is characterized by facial rash (poikiloderma, a diagnostic hallmark), growth retardation, sparse scalp hair/eyelashes/eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, and a predisposition to cancer. There are two clinical forms: type I, which is characterized by poikiloderma, ectodermal dysplasia, and juvenile cataracts with unknown etiology, and type II which is characterized by poikiloderma, congenital bone defects, an increased frequency of malignancy (especially osteosarcoma), and RECQL4 (8q24.3) mutation.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> To date, around 400 cases have been reported.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Here, the authors report a case of poikiloderma and growth retardation in a Chinese girl presenting two RECQL4 mutations in a novel, compound heterozygous arrangement (c.2492_2493del and c.1391-2A>C) recorded <span class="elsevierStyleItalic">via</span> mutational screening, which is the first reported in RTS.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The proband is a 2-year-old girl with poikiloderma bilaterally on her face and ears. Her parents complained that their younger daughter showed erythema, swelling, and blistering bilaterally on her face since the age of 6 months, which gradually developed to reticulated hypo- and hyperpigmentation. The girl also presented with thinning of eyebrows, photosensitivity, and gastrointestinal problems including chronic emesis or diarrhea. Neither her parents nor her 5-year-old sister has similar symptoms. The patient was born at full term with a mild toe abnormality. However, slow weight gain, short stature, and teeth retardation were noted on a physical examination. The dermatological examination found bilateral depigmentation, hyperpigmentation, punctate atrophy, and telangiectasia over the patient's face and ears (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Bone mineral density measurement was performed at 1 year of age, which showed low bone mineral density. Her cognitive ability, ophthalmic testing, and other examination results were within normal limits and no other alterations were found.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">For differential molecular diagnosis of poikiloderma, targeted exome sequencing was performed. Mutational screening for BLM, the defective gene in Bloom's syndrome and other poikiloderma-related diseases, was negative. Gene sequencing revealed two distinct heterozygous mutations on the RECQL4 gene (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). One of them is a point mutation located in exon 9, consisting of a change of adenine for cytosine (c.1391-2A>C), which was found in her unaffected father and sister. This mutation has not been reported, but the possible effect on the protein through a splice acceptor variant can be assumed. On the other allele, the mutation is a deletion of two nucleotides found in exon 16 (c.2492_2493delAT), which produces a frame shift (p.His831Argfs); this mutation is known to be rare and last evaluated by Kitao et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> This mutation was found in her unaffected mother. These two mutations of the proband respectively come from her father and mother, known as compound heterozygous mutations, and accord with the autosomal recessive inheritance law. Her sister only presents c.1391-2A>C, which is a heterozygous mutation and, theoretically, she won’t show any symptoms.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The patient reported here has the clinical signs like poikiloderma, sparse eyebrows, small stature, dental abnormality, and mild skeletal abnormality, which are mentioned in the previous articles.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> No cataracts and cancer have been found so far. Unlike other previous cases, the lesion doesn’t affect her extremities, and the authors consider that she is too young to show all the symptoms. RTS was diagnosed according to typical lesion and mutation of RECQL4 gene, and the patient was advised to avoid sun exposure and undergo annual checkups for the eyes, skin, and bones.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The novels compound heterozygous RECQL4 mutations presented in this patient is the first reported in RTS. Loss of RECQL4 protein function occurs in approximately two-thirds of RTS patients and is associated with risk of osteosarcoma.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Further functional studies to confirm the protein-damaging effect are needed to proceed. Poikiloderma is a symptom of many systemic diseases, such as lupus erythematosus, Bloom syndrome, Kindler syndrome, and dyskeratosis congenita. The result of genetic testing is instructive and meaningful to a definitive diagnosis and future procreation guidance for the patient's family.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Financial support</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors’ contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Xinyue Zhang: Drafting and editing of the manuscript.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Songmei Geng: Approval of final version of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Yi Zheng: Critical review of the literature.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-01-12" "fechaAceptado" => "2019-10-04" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">How to cite this article: Zhang X, Geng S, Zheng Y. Rare presentation of Rothmund-Thomson syndrome with novel compound heterozygous mutations of the RECQL4 gene. An Bras Dermatol. 2020;95:538–40.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Department of Dermatology, Second Affiliated Hospital, Xi’An Jiaotong University, Shaanxi, China.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 1674 "Tamanyo" => 304293 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Poikiloderma in a patient with RTS. Depigmentation, hyperpigmentation, punctate atrophy, telangiectasia, and loss of eyebrows are seen bilaterally on the face.</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" => 1413 "Ancho" => 2079 "Tamanyo" => 268529 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Two novel heterozygous variants in the RECQL4 gene confirmed by gene sequencing. One was in the splice site, c.1391-2A>C from her father, and also was seen in her sister. The other was a deletion mutation, c.2492_2493delAT (p.His831Argfs) from her mother.</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. Larizza" 1 => "G. Roversi" 2 => "L. 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|---|---|---|---|
| 2024 November | 17 | 10 | 27 |
| 2024 October | 101 | 80 | 181 |
| 2024 September | 144 | 72 | 216 |
| 2024 August | 170 | 101 | 271 |
| 2024 July | 136 | 107 | 243 |
| 2024 June | 130 | 66 | 196 |
| 2024 May | 142 | 74 | 216 |
| 2024 April | 138 | 77 | 215 |
| 2024 March | 97 | 57 | 154 |
| 2024 February | 93 | 79 | 172 |
| 2024 January | 61 | 52 | 113 |
| 2023 December | 55 | 58 | 113 |
| 2023 November | 73 | 72 | 145 |
| 2023 October | 59 | 74 | 133 |
| 2023 September | 81 | 76 | 157 |
| 2023 August | 64 | 43 | 107 |
| 2023 July | 60 | 31 | 91 |
| 2023 June | 69 | 47 | 116 |
| 2023 May | 49 | 30 | 79 |
| 2023 April | 45 | 33 | 78 |
| 2023 March | 65 | 49 | 114 |
| 2023 February | 46 | 34 | 80 |
| 2023 January | 47 | 47 | 94 |
| 2022 December | 56 | 24 | 80 |
| 2022 November | 75 | 48 | 123 |
| 2022 October | 72 | 45 | 117 |
| 2022 September | 56 | 72 | 128 |
| 2022 August | 45 | 45 | 90 |
| 2022 July | 38 | 55 | 93 |
| 2022 June | 43 | 68 | 111 |
| 2022 May | 39 | 72 | 111 |
| 2022 April | 36 | 48 | 84 |
| 2022 March | 49 | 66 | 115 |
| 2022 February | 18 | 32 | 50 |
| 2022 January | 53 | 75 | 128 |
| 2021 December | 40 | 59 | 99 |
| 2021 November | 40 | 56 | 96 |
| 2021 October | 51 | 79 | 130 |
| 2021 September | 36 | 39 | 75 |
| 2021 August | 41 | 48 | 89 |
| 2021 July | 35 | 44 | 79 |
| 2021 June | 36 | 62 | 98 |
| 2021 May | 49 | 81 | 130 |
| 2021 April | 120 | 285 | 405 |
| 2021 March | 101 | 54 | 155 |
| 2021 February | 60 | 25 | 85 |
| 2021 January | 73 | 21 | 94 |
| 2020 December | 36 | 20 | 56 |
| 2020 November | 27 | 15 | 42 |
| 2020 October | 15 | 9 | 24 |
| 2020 September | 29 | 16 | 45 |
| 2020 August | 9 | 14 | 23 |
| 2020 July | 30 | 15 | 45 |
| 2020 June | 15 | 11 | 26 |
| 2020 May | 3 | 5 | 8 |
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