Letter to the Editor
TSC2/PKD1 contiguous gene syndrome
Síndrome de genes contiguos TSC2/PKD1
Francisco Cammarata-Scalisia,
, Concha Vidales Morenob, Carmen Zara-Chirinosc, Ana Brachoc, Diomar Pérezd
Corresponding author
a Unidad de Genética Médica, Departamento de Puericultura y Pediatría, Facultad de Medicina, Universidad de Los Andes, Mérida, Venezuela
b Área Diagnóstica, DNA Data, San Sebastián, Guipúzcoa, Spain
c Instituto de Investigaciones Genéticas, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
d Estudiante de Medicina, Facultad de Medicina, Universidad de Los Andes, Mérida, Venezuela
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Spanish nephrologists survey" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "665" "paginaFinal" => "668" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Barreras para el desarrollo de la hemodiálisis domiciliaria en España. 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Her parents were healthy and not consanguineous. She was born as a result of her mother's second pregnancy, an unmonitored single-foetus pregnancy complicated by HELLP syndrome. She was delivered by Caesarian section after 36 weeks, required resuscitation at birth and had generalised cyanosis. Her birth weight was 1700<span class="elsevierStyleHsp" style=""></span>g (DE −3.8) and her birth length was 46<span class="elsevierStyleHsp" style=""></span>cm (DE −2.5). She was hospitalised at 8 months of age due to tonic–clonic seizures, followed a torpid course with global delay in maturation delay.</p><p id="par0010" class="elsevierStylePara elsevierViewall">On physical examination, she had a tendency towards dolichocephaly with an unusual facies characterised by a prominent forehead; a concave nasal bridge with a flattened tip; upturned nostrils; and a short, wide philtrum. She had 7 hypochromic lesions; 2 were ash-leaf that corresponds to the largest in her lumbar region and on her left thigh (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">An MRI scan showed patch-shaped multi-focal areas with hyperintense behaviour on T2 flair in both parietal hemispheres not leading to a mass effect on the surrounding structures. A sleep electroencephalogram was abnormal due to paroxysmal activity with bursts of points and acute waves in the fronto-polar and right temporal regions. An eye ultrasound showed a raised lesion with a hypoechoic internal structure in the papillary area, consistent with an astrocytic hamartoma of the optic nerve of the right eye. A transthoracic echocardiogram showed tumour in the right ventricular outflow tract suggestive of rhabdomyoma neither causing obstruction nor resulting in haemodynamic repercussions. A kidney ultrasound showed an increase in volume in both kidneys, 9.4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4.0<span class="elsevierStyleHsp" style=""></span>cm for the left kidney and 9<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3.6<span class="elsevierStyleHsp" style=""></span>cm for the right kidney. It revealed the formation of fluid-filled cysts, some of which had thick walls. The largest one, in the lower pole of the right kidney, was 6<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3.1<span class="elsevierStyleHsp" style=""></span>cm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b). A kidney profile, as well as other serum analysis, was found to be within the reference values.</p><p id="par0020" class="elsevierStylePara elsevierViewall">DNA was extracted, and mass sequencing of the <span class="elsevierStyleItalic">TSC1</span> and <span class="elsevierStyleItalic">TSC2</span> genes was performed on the MiSeq (Illumina) platform. This revealed 2 polymorphisms in heterozygosis in <span class="elsevierStyleItalic">TSC1</span>, GAA/GAG, c.1335A>G, p.Glu445Glu and ATG/ACG, c.965T>C, p.Met322Thr with rs7862221 and rs1073123 references, respectively. A multiplex ligation-dependent probe amplification study (MLPA P337) showed a deletion in heterozygosis of the probes located in exons 10–42 of the <span class="elsevierStyleItalic">TSC2</span> gene, as well as exons 30 and 40 of the <span class="elsevierStyleItalic">PKD1</span> gene (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Tuberous sclerosis complex (OMIM #<a href="omim:191100">191100</a> and #<a href="omim:613254">613254</a>) is a multi-system disorder that exhibits an autosomal dominant inheritance pattern. It is characterised by multiple hamartomas of the brain, eyes, heart, kidneys and skin.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1–3</span></a> It has a broad, variable phenotypic spectrum that includes seizures, intellectual disability and kidney and skin abnormalities, as well as an increased risk of malignancy.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,4</span></a> Its incidence is one in every 6000–11,000 live births.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> It is due to mutations in the <span class="elsevierStyleItalic">TSC1</span> (OMIM #<a href="omim:605284">605284</a>) and <span class="elsevierStyleItalic">TSC2</span> (OMIM #<a href="omim:191092">191092</a>) tumour suppressor genes, which encode hamartin and tuberin, respectively.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a> The latter gene is located in 16p13.3 adjacent to the <span class="elsevierStyleItalic">PKD1</span> gene (OMIM #<a href="omim:601313">601313</a>), responsible for 85% of cases of polycystic kidney disease (OMIM #<a href="omim:173900">173900</a>), which also has an autosomal dominant inheritance pattern.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,5</span></a> This is the most common hereditary kidney disorder, with an incidence of one in every 400–1000 live births.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A large deletion which may encompass the genes <span class="elsevierStyleItalic">TSC2</span> and <span class="elsevierStyleItalic">PKD1</span> causes so-called <span class="elsevierStyleItalic">TSC2</span>/<span class="elsevierStyleItalic">PKD1</span> contiguous gene syndrome (OMIM #<a href="omim:600273">600273</a>).<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,2,5</span></a> It was first reported by Brook-Carter et al. in 1994 in 6 patients with tuberous sclerosis complex with severe childhood polycystic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> It is characterised by large bilateral kidney cysts. These cysts may be congenital or of very early onset, which may alter the disease prognosis. It has been estimated that 5% of patients with tuberous sclerosis complex have polycystic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Kidney complications represent the second leading cause of death after neurological impairment in tuberous sclerosis complex. Angiomyolipomas are the most common kidney abnormality in adults and children, and may be present in 16% of cases, in addition to small cysts and renal cell carcinoma.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We present the case of a girl with a genetic and clinical diagnosis of <span class="elsevierStyleItalic">TSC2/PKD1</span> contiguous gene syndrome, with an emphasis on multidisciplinary assessment given her pleiotropy and disease severity, as well as appropriate genetic counselling with a 50% risk of recurrence in descendants of affected individuals.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Cammarata-Scalisi F, Vidales Moreno C, Zara-Chirinos C, Bracho A, Pérez D. Síndrome de genes contiguos <span class="elsevierStyleItalic">TSC2</span>/<span class="elsevierStyleItalic">PKD1</span>. Nefrologia. 2017;37:663–665.</p>" ] ] "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" => 1101 "Ancho" => 2500 "Tamanyo" => 205613 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) A hypochromic ash-leaf lesion on the patient's left thigh; (b) a kidney ultrasound showed an increase in volume in both kidneys and multiple bilateral cysts.</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" => 2304 "Ancho" => 2833 "Tamanyo" => 420858 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An MLPA P337 study showed a deletion in heterozygosis in exons 10–42 of the <span class="elsevierStyleItalic">TSC2</span> gene, as well as exons 30 and 40 of the <span class="elsevierStyleItalic">PKD1</span> gene.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">TSC2</span>/<span class="elsevierStyleItalic">PKD1</span> contiguous gene deletion syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 6 | 12 |
| 2024 October | 54 | 42 | 96 |
| 2024 September | 58 | 42 | 100 |
| 2024 August | 78 | 68 | 146 |
| 2024 July | 62 | 45 | 107 |
| 2024 June | 82 | 50 | 132 |
| 2024 May | 52 | 40 | 92 |
| 2024 April | 61 | 35 | 96 |
| 2024 March | 50 | 34 | 84 |
| 2024 February | 45 | 44 | 89 |
| 2024 January | 68 | 62 | 130 |
| 2023 December | 65 | 35 | 100 |
| 2023 November | 70 | 39 | 109 |
| 2023 October | 63 | 79 | 142 |
| 2023 September | 59 | 39 | 98 |
| 2023 August | 49 | 36 | 85 |
| 2023 July | 48 | 41 | 89 |
| 2023 June | 55 | 24 | 79 |
| 2023 May | 50 | 46 | 96 |
| 2023 April | 25 | 25 | 50 |
| 2023 March | 63 | 25 | 88 |
| 2023 February | 41 | 20 | 61 |
| 2023 January | 56 | 43 | 99 |
| 2022 December | 74 | 28 | 102 |
| 2022 November | 56 | 43 | 99 |
| 2022 October | 65 | 36 | 101 |
| 2022 September | 69 | 34 | 103 |
| 2022 August | 52 | 59 | 111 |
| 2022 July | 30 | 56 | 86 |
| 2022 June | 52 | 43 | 95 |
| 2022 May | 47 | 27 | 74 |
| 2022 April | 73 | 44 | 117 |
| 2022 March | 46 | 46 | 92 |
| 2022 February | 78 | 47 | 125 |
| 2022 January | 62 | 42 | 104 |
| 2021 December | 65 | 41 | 106 |
| 2021 November | 54 | 33 | 87 |
| 2021 October | 76 | 40 | 116 |
| 2021 September | 66 | 46 | 112 |
| 2021 August | 61 | 54 | 115 |
| 2021 July | 45 | 51 | 96 |
| 2021 June | 59 | 21 | 80 |
| 2021 May | 64 | 47 | 111 |
| 2021 April | 162 | 77 | 239 |
| 2021 March | 62 | 31 | 93 |
| 2021 February | 48 | 39 | 87 |
| 2021 January | 56 | 30 | 86 |
| 2020 December | 36 | 18 | 54 |
| 2020 November | 26 | 17 | 43 |
| 2020 October | 26 | 17 | 43 |
| 2020 September | 29 | 14 | 43 |
| 2020 August | 39 | 15 | 54 |
| 2020 July | 25 | 30 | 55 |
| 2020 June | 21 | 39 | 60 |
| 2020 May | 52 | 22 | 74 |
| 2020 April | 41 | 14 | 55 |
| 2020 March | 64 | 25 | 89 |
| 2020 February | 37 | 17 | 54 |
| 2020 January | 41 | 27 | 68 |
| 2019 December | 33 | 23 | 56 |
| 2019 November | 35 | 24 | 59 |
| 2019 October | 27 | 16 | 43 |
| 2019 September | 30 | 21 | 51 |
| 2019 August | 31 | 24 | 55 |
| 2019 July | 30 | 21 | 51 |
| 2019 June | 25 | 42 | 67 |
| 2019 May | 38 | 88 | 126 |
| 2019 April | 70 | 86 | 156 |
| 2019 March | 60 | 34 | 94 |
| 2019 February | 40 | 38 | 78 |
| 2019 January | 38 | 17 | 55 |
| 2018 December | 73 | 59 | 132 |
| 2018 November | 114 | 32 | 146 |
| 2018 October | 67 | 14 | 81 |
| 2018 September | 71 | 26 | 97 |
| 2018 August | 60 | 16 | 76 |
| 2018 July | 55 | 14 | 69 |
| 2018 June | 55 | 13 | 68 |
| 2018 May | 51 | 18 | 69 |
| 2018 April | 56 | 10 | 66 |
| 2018 March | 44 | 12 | 56 |
| 2018 February | 35 | 9 | 44 |
| 2018 January | 44 | 9 | 53 |
| 2017 December | 50 | 10 | 60 |
| 2017 November | 12 | 1 | 13 |
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