title: Dynamic modification strategy of the Israeli carrier screening protocol: inclusion of the Oriental Jewish Group to the cystic fibrosis panel.
abstract: OBJECTIVE
  A retrospective population study was conducted to determine the carrier frequencies of recently identified mutations in Oriental Jewish cystic fibrosis patients.
  
  
  METHODS
  Data were collected from 10 medical centers that screened the following mutations: two splice site mutations-3121-1G>A and 2751 + 1insT-and one nonsense mutation-the Y1092X in Iraqi Jews. One missense mutation, I1234V, was screened in Yemenite Jews.
  
  
  RESULTS
  A total of 2499 Iraqi Jews were tested for one, two, or all three mutations. The 3121-1G>A, Y1092X, and 2751 + 1insT mutations had a carrier frequency of 1:68.5, 1:435, and 0, respectively. In 1435 Yemenite Jews screened, I1234V had a carrier frequency of 1:130.
  
  
  CONCLUSIONS
  The 0.84% allele frequency of the three Iraqi founder mutations falls within the Israeli Society of Medical Geneticists' inclusion criteria for screening of 1:60 carrier frequency; hence, Iraqi Jews were added to the carrier screening policy with a panel including the three Iraqi founder mutations in addition to the five Ashkenazi mutations previously detected in Eastern Jews. 2751 + 1insT that was detected in patients only was included in the screening panel to increase the detection rate. I1234V does not meet the inclusion criteria but is now offered on a diagnostic basis and can be added to the screening panel for individuals whose mixed origin includes Yemenite, in addition to protocol-recommended origins. This study demonstrates the dynamic modifications of the Israeli carrier cystic fibrosis screening protocol based on newly detected founder mutations in a large cohort, taking into account mutation impact and intercommunal admixture.
authors.affiliation: Genetics Institute, Assaf Harofeh Medical Center, Zerifin, Israel. oreish@post.tau.ac.il
authors.forename: Orit
authors.initials: O
authors.lastname: Reish
authors.forename: Zvi U
authors.initials: ZU
authors.lastname: Borochowitz
authors.forename: Vardit
authors.initials: V
authors.lastname: Adir
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Mazal
authors.initials: M
authors.lastname: Karpati
authors.forename: Atalia
authors.initials: A
authors.lastname: Shtorch
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
authors.forename: Stavit
authors.initials: S
authors.lastname: Shalev
authors.forename: Fuad
authors.initials: F
authors.lastname: Fares
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: Tzipora C
authors.initials: TC
authors.lastname: Falik-Zaccai
authors.forename: Daphne
authors.initials: D
authors.lastname: Chapman-Shimshoni
mesh_terms: D003550:Cystic Fibrosis / Q000208:ethnology* / Q000235:genetics; D005787:Gene Frequency; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007557:Israel / Q000208:ethnology; D007585:Jews / Q000235:genetics*; D009154:Mutation; D044382:Population Groups / Q000235:genetics; D012189:Retrospective Studies