Novel MLH1 duplication identified in Colombian families with Lynch syndrome

Virginia Alonso-Espinaco, María Dolores Giráldez, Carlos Trujillo, Heleen Van Der Klift, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Irene Madrigal, Angela M. Jones, M. Magdalena Echeverry, Alejandro Velez, Ian Tomlinson, Montserrat Milà, Juul Wijnen, Luis Carvajal-Carmona, Antoni Castells, Sergi Castellví-Bel

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose: Lynch syndrome accounts for 2-4% of all colorectal cancer, and is mainly caused by germline mutations in the DNA mismatch repair genes. Our aim was to characterize the genetic mutation responsible for Lynch syndrome in an extensive Colombian family and to study its prevalence in Antioquia. Methods: A Lynch syndrome family fulfilling Amsterdam criteria II was studied by immunohistochemistry and by multiplex ligation-dependent probe amplification (MLPA). Results were confirmed by additional independent MLPA, Southern blotting, and sequencing. Results: Index case tumor immunohistochemistry results were MLH1-, MSH2+, MSH6+, and PMS2-. MLPA analysis detected a duplication of exons 12 and 13 of MLH1. This mutation was confirmed and characterized precisely to span 4219 base pairs. Duplication screening in this family led to the identification of six additional carriers and 13 noncarriers. We also screened 123 early-onset independent colorectal cancer cases from the same area and identified an additional unrelated carrier. CONCLUSION:: A novel duplication of exons 12 and 13 of the MLH1 gene was detected in two independent Lynch syndrome families from Colombia. A putative founder effect and prescreening Lynch syndrome Antioquia families for this specific mutation before thorough mismatch repair mutational screening could be suggested.

Original languageEnglish (US)
Pages (from-to)155-160
Number of pages6
JournalGenetics in Medicine
Volume13
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Hereditary Nonpolyposis Colorectal Neoplasms
Multiplex Polymerase Chain Reaction
DNA Mismatch Repair
Mutation
Colorectal Neoplasms
Exons
Immunohistochemistry
Founder Effect
Colombia
Germ-Line Mutation
Southern Blotting
Base Pairing
Genes
Cross-Sectional Studies
Neoplasms

Keywords

  • Colombia
  • hereditary cancer
  • HNPCC
  • Lynch syndrome
  • MMR genes

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Alonso-Espinaco, V., Giráldez, M. D., Trujillo, C., Van Der Klift, H., Muñoz, J., Balaguer, F., ... Castellví-Bel, S. (2011). Novel MLH1 duplication identified in Colombian families with Lynch syndrome. Genetics in Medicine, 13(2), 155-160. https://doi.org/10.1097/GIM.0b013e318202e10b

Novel MLH1 duplication identified in Colombian families with Lynch syndrome. / Alonso-Espinaco, Virginia; Giráldez, María Dolores; Trujillo, Carlos; Van Der Klift, Heleen; Muñoz, Jenifer; Balaguer, Francesc; Ocaña, Teresa; Madrigal, Irene; Jones, Angela M.; Echeverry, M. Magdalena; Velez, Alejandro; Tomlinson, Ian; Milà, Montserrat; Wijnen, Juul; Carvajal-Carmona, Luis; Castells, Antoni; Castellví-Bel, Sergi.

In: Genetics in Medicine, Vol. 13, No. 2, 02.2011, p. 155-160.

Research output: Contribution to journalArticle

Alonso-Espinaco, V, Giráldez, MD, Trujillo, C, Van Der Klift, H, Muñoz, J, Balaguer, F, Ocaña, T, Madrigal, I, Jones, AM, Echeverry, MM, Velez, A, Tomlinson, I, Milà, M, Wijnen, J, Carvajal-Carmona, L, Castells, A & Castellví-Bel, S 2011, 'Novel MLH1 duplication identified in Colombian families with Lynch syndrome', Genetics in Medicine, vol. 13, no. 2, pp. 155-160. https://doi.org/10.1097/GIM.0b013e318202e10b
Alonso-Espinaco V, Giráldez MD, Trujillo C, Van Der Klift H, Muñoz J, Balaguer F et al. Novel MLH1 duplication identified in Colombian families with Lynch syndrome. Genetics in Medicine. 2011 Feb;13(2):155-160. https://doi.org/10.1097/GIM.0b013e318202e10b
Alonso-Espinaco, Virginia ; Giráldez, María Dolores ; Trujillo, Carlos ; Van Der Klift, Heleen ; Muñoz, Jenifer ; Balaguer, Francesc ; Ocaña, Teresa ; Madrigal, Irene ; Jones, Angela M. ; Echeverry, M. Magdalena ; Velez, Alejandro ; Tomlinson, Ian ; Milà, Montserrat ; Wijnen, Juul ; Carvajal-Carmona, Luis ; Castells, Antoni ; Castellví-Bel, Sergi. / Novel MLH1 duplication identified in Colombian families with Lynch syndrome. In: Genetics in Medicine. 2011 ; Vol. 13, No. 2. pp. 155-160.
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AU - Balaguer, Francesc

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AU - Madrigal, Irene

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AU - Velez, Alejandro

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AU - Milà, Montserrat

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