Rothmund-Thomson syndrome

Elisa A. Colombo, Andrea Locatelli, Laura Cubells Sánchez, Sara Romeo, Nursel H. Elcioglu, Isabelle Maystadt, Altea Esteve Martínez, Alessandra Sironi, Laura Fontana, Palma Finelli, Cristina Gervasini, Vanna Pecile, Lidia Larizza

Research output: Contribution to journalArticle

Abstract

Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogenic RECQL4 variants by in silico predictions and transcripts analyses. Complete phenotype of patients #39 and #42 whose affected siblings developed osteosarcoma correlates with their c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G>C;1573delT], c.[3021_3022del] variants which damage the helicase domain. Literature survey highlights enrichment of these variants affecting the helicase domain in patients with cancer outcome raising the issue of strict oncological surveillance. Conversely, patients #29 and #19 have a mild phenotype and carry, respectively, the unreported homozygous c.3265G>T and c.3054A>G variants, both sparing the helicase domain. Finally, despite matching several criteria for RTS clinical diagnosis, patient #38 is heterozygous for c.2412_2414del, no pathogenic CNVs out of those evidenced by high-resolution CGH-array, emerged as contributors to her phenotype.
Original languageItalian
JournalInternational Journal of Molecular Sciences
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 6 2018

Cite this

Colombo, E. A., Locatelli, A., Sánchez, L. C., Romeo, S., Elcioglu, N. H., Maystadt, I., ... Larizza, L. (2018). Rothmund-Thomson syndrome. International Journal of Molecular Sciences, 19(4). https://doi.org/10.3390/ijms19041103

Rothmund-Thomson syndrome. / Colombo, Elisa A.; Locatelli, Andrea; Sánchez, Laura Cubells; Romeo, Sara; Elcioglu, Nursel H.; Maystadt, Isabelle; Martínez, Altea Esteve; Sironi, Alessandra; Fontana, Laura; Finelli, Palma; Gervasini, Cristina; Pecile, Vanna; Larizza, Lidia.

In: International Journal of Molecular Sciences, Vol. 19, No. 4, 06.04.2018.

Research output: Contribution to journalArticle

Colombo, EA, Locatelli, A, Sánchez, LC, Romeo, S, Elcioglu, NH, Maystadt, I, Martínez, AE, Sironi, A, Fontana, L, Finelli, P, Gervasini, C, Pecile, V & Larizza, L 2018, 'Rothmund-Thomson syndrome', International Journal of Molecular Sciences, vol. 19, no. 4. https://doi.org/10.3390/ijms19041103
Colombo EA, Locatelli A, Sánchez LC, Romeo S, Elcioglu NH, Maystadt I et al. Rothmund-Thomson syndrome. International Journal of Molecular Sciences. 2018 Apr 6;19(4). https://doi.org/10.3390/ijms19041103
Colombo, Elisa A. ; Locatelli, Andrea ; Sánchez, Laura Cubells ; Romeo, Sara ; Elcioglu, Nursel H. ; Maystadt, Isabelle ; Martínez, Altea Esteve ; Sironi, Alessandra ; Fontana, Laura ; Finelli, Palma ; Gervasini, Cristina ; Pecile, Vanna ; Larizza, Lidia. / Rothmund-Thomson syndrome. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 4.
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AU - Locatelli, Andrea

AU - Sánchez, Laura Cubells

AU - Romeo, Sara

AU - Elcioglu, Nursel H.

AU - Maystadt, Isabelle

AU - Martínez, Altea Esteve

AU - Sironi, Alessandra

AU - Fontana, Laura

AU - Finelli, Palma

AU - Gervasini, Cristina

AU - Pecile, Vanna

AU - Larizza, Lidia

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N2 - Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogenic RECQL4 variants by in silico predictions and transcripts analyses. Complete phenotype of patients #39 and #42 whose affected siblings developed osteosarcoma correlates with their c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G>C;1573delT], c.[3021_3022del] variants which damage the helicase domain. Literature survey highlights enrichment of these variants affecting the helicase domain in patients with cancer outcome raising the issue of strict oncological surveillance. Conversely, patients #29 and #19 have a mild phenotype and carry, respectively, the unreported homozygous c.3265G>T and c.3054A>G variants, both sparing the helicase domain. Finally, despite matching several criteria for RTS clinical diagnosis, patient #38 is heterozygous for c.2412_2414del, no pathogenic CNVs out of those evidenced by high-resolution CGH-array, emerged as contributors to her phenotype.

AB - Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogenic RECQL4 variants by in silico predictions and transcripts analyses. Complete phenotype of patients #39 and #42 whose affected siblings developed osteosarcoma correlates with their c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G>C;1573delT], c.[3021_3022del] variants which damage the helicase domain. Literature survey highlights enrichment of these variants affecting the helicase domain in patients with cancer outcome raising the issue of strict oncological surveillance. Conversely, patients #29 and #19 have a mild phenotype and carry, respectively, the unreported homozygous c.3265G>T and c.3054A>G variants, both sparing the helicase domain. Finally, despite matching several criteria for RTS clinical diagnosis, patient #38 is heterozygous for c.2412_2414del, no pathogenic CNVs out of those evidenced by high-resolution CGH-array, emerged as contributors to her phenotype.

KW - Clinical expressivity

KW - Osteosarcoma outcome

KW - RECQL4

KW - Rothmund-Thomson syndrome

KW - Transcript analysis

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