Rothmund-Thomson syndrome: Insights from new patients on the genetic variability underpinning clinical presentation and cancer outcome

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 languageEnglish
Article number1103
JournalInternational Journal of Molecular Sciences
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 6 2018

Fingerprint

Rothmund-Thomson Syndrome
phenotype
Genes
cancer
Phenotype
Neoplasms
damage
genome
Osteosarcoma
mutations
surveillance
genes
Computer Simulation
Siblings
Genome
Mutation
causes
high resolution
predictions

Keywords

  • Clinical expressivity
  • Osteosarcoma outcome
  • RECQL4
  • Rothmund-Thomson syndrome
  • Transcript analysis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Rothmund-Thomson syndrome : Insights from new patients on the genetic variability underpinning clinical presentation and cancer outcome. / 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, 1103, 06.04.2018.

Research output: Contribution to journalArticle

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 : Insights from new patients on the genetic variability underpinning clinical presentation and cancer outcome. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 4.
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