title: American founder mutation for Lynch syndrome. Prevalence estimates and implications.
abstract: BACKGROUND
  Recently, a new founder mutation, an exon 1-6 deletion in a mismatch repair gene (MMR), MSH2, in nine kindreds with Lynch syndrome was reported. In 3 of the kindreds this mutation was traced by genealogy through 11-12 generations to a common founder, and thus termed the American Founder Mutation (AFM). Since then, 13 additional 'unrelated' kindreds with AFM were detected by a recently designed single polymerase chain reaction. This test might serve as first-line screening for Lynch syndrome mutations, provided AFM was prevalent, which is assessed in the current study.
  
  
  METHODS
  The number of current AFM carriers and the incidence of Lynch syndrome caused by AFM were estimated based on population growth of mutation carriers derived from genealogy data. For cross-checking, its annual incidence was also estimated based on published epidemiology data.
  
  
  RESULTS
  There are 18,981 (5th and 95th percentiles, 6038 and 34,466, respectively) expected current AFM carriers, or 160 (range 51-290) Lynch syndrome cases diagnosed per year due to AFM estimated based on genealogy data. The incidence estimate closely overlaps with that based on published epidemiology data, which is 114-400 cases per year.
  
  
  CONCLUSIONS
  A large number of AFM carriers are likely to exist in the U.S., which harbors significant implications for cancer control. Given the ease of detection, testing for AFM not only among members of the existing AFM families, but also among all patients with Lynch syndrome in the U.S. is proposed.
authors.affiliation: Department of Preventive Medicine and Public Health, Creighton University, Omaha, Nebraska 68178, USA. htlynch@creighton.edu
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: Heather
authors.initials: H
authors.lastname: Hampel
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Jane F
authors.initials: JF
authors.lastname: Lynch
authors.forename: Ross
authors.initials: R
authors.lastname: Okimoto
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Clark
authors.forename: Stephanie
authors.initials: S
authors.lastname: Coronel
authors.forename: Abdon
authors.initials: A
authors.lastname: Trowonou
authors.forename: Yun-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Gleb R
authors.initials: GR
authors.lastname: Haynatzki
authors.forename: Gordon
authors.initials: G
authors.lastname: Gong
mesh_terms: D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D015995:Prevalence; D014481:United States