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Purpose: 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., Conclusion: 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.

We describe the molecular analysis of a large three generation Palestinian family segregating for monilethrix. Previous reports have shown that mutations in type-II hair cortex keratin genes, hHb1 and hHb6, are associated with monilethrix. Genetic linkage analysis performed on this family using markers flanking the hHb6 gene exhibited strong evidence for linkage. Sequence analysis revealed a nucleotide substitution of G --> T at nucleotide 1230 resulting in a glutamic acid to aspartic acid amino acid substitution at codon 410, identical to that reported in a French family. The family in our study provides further evidence that mutations of the hHb6 gene are responsible for monilethrix.