Cystic Fibrosis testing among Arab-Americans

Abstract

Purpose: Limited data regarding the cystic fibrosis carrier frequency and mutation detection rate is available for Arab-Americans. We retrospectively determined the frequency of carriers among Arab-Americans undergoing preconception and prenatal carrier screening in our laboratories. Methods: Between October, 2001 and June, 2005, we performed carrier screening on 805 Arab-Americans, testing for at least the original 25 mutations recommended by the American College of Medical Genetics. We compared our results to previously published studies among Arabic cystic fibrosis patients. We also performed diagnostic testing on seven individuals.Results: Seven carriers were identified, with an observed carrier frequency of 1 in 115. The most common mutation we identified was W1282X (57% of the mutations detected), followed by ⌬F508 and R117H. Three of 7 patients with a known or suspected diagnosis had two identifiable mutations, including 1548delG, ⌬F508, W1282X, 2789 ϩ 5GϾA and R170H. Conclusion: The current recommended carrier screening panel includes only six mutations reported among Arabic cystic fibrosis patients, accounting for 37.1% of the mutations identified among this group. The addition of 1548delG, I1234V, H139L and 4010del4 as part of an extended screening panel would increase the detection rate to 66.3%, similar to the mutation detection rates in other races/ethnic groups. Genet Med 2006:8(4):255-258. Key Words: cystic fibrosis, Arab-American, carrier screeningSince the cloning of the cystic fibrosis (CF) gene in 1989, 1,2,3 more than 1,000 mutations have been identified. 4 Most are extremely rare, often reported in only one family. In 2001, the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG) recommended CF carrier screening using a 25-mutation panel for Caucasians who are pregnant or considering pregnancy. They also recommended that testing be made available to individuals in other races and ethnic groups with a lower CF carrier frequency. 5 The original 25 mutations were chosen because they had a frequency of Ն0.1% in the pan-ethnic U.S. population. 5 This panel was modified in 2004 to 23 mutations. 6 Reliable data exist for the carrier frequency and mutation detection rates among Caucasians, African-Americans, and Hispanic-Americans. This is essential for accurate interpretation and risk assessment used by patients to make informed decisions regarding reproductive options. 6,7 However, there is limited epidemiological data on the frequency of CF and prevalent mutations among Arabic CF patients. Furthermore, there are no published reports describing the outcome of CF carrier screening among Arab-Americans. Detroit, Michigan has one of the largest Arab-American populations. Arab-Americans comprise the third largest population tested in our laboratories, after Caucasians and African-Americans. We report our experience with CF carrier screening among Arab-Americans and compare our results to previously published studies among Arabic CF patients. MATER...

Mutational spectrum of cystic fibrosis in the Lebanese population

“…Interestingly, the two common Arab mutations 1548delG and H139L, which were not found in any Caucasian chromosomes and were suggested to originate from the native Arab population, were absent from our study [15,28]. A possible explanation to differences between our results and those reported from other Arab studies may be due to the heterogeneous backgrounds of our families in contrast to the more pure Arab homogenous background from other studies [25].…”

“…F508del was not as frequently reported in the Arab populations. Moreover, Arabs carry CFTR mutations that were never described in the Caucasians [15]. In this study, we describe the CFTR mutational spectrum in the Lebanese population.…”

Cystic fibrosis: A new mutation in the Lebanese population

“…Recently, a panel of 11 common mutations accounting overall for 70% of all Arab CF chromosomes have been reported : ΔF508del, 3120 + 1G " A, N1303K, W1282X, G115X, 711 + 1G " A, S549R, I1234V, 1548delG , H139L and 4010del4 [9]. The latter three mutations are believed to have originated in the Arab native populations since they were never described in Caucasian CF patients [5][6][7][8].…”

“…Few studies have reported on Arab populations in general and only one study was conducted on the Lebanese population [4]. According to these reports, while ΔF508del mutation does not seem to account for more than 20% of all Caucasian CF chromosomes, several other mutations described in Arabs have never been described elsewhere [5][6][7][8][9].…”

Epidemiology and genetics of cystic fibrosis in Asia: In preparation for the next‐generation treatments

“…Data suggest that more than 160 CFTR variants have been identified on approximately 3700 Asian CF chromosomes. Overall, F508del (p.Phe508del, c.1521_1523delCTT) remains the most common variant in Asian countries with few exceptions (Table ) . However, F508del constitutes only 12–31% of Asian CF alleles compared with 66% in the worldwide CF population comprised mainly from North America, Europe, Canada, Australia and New Zealand (http://www.genet.sickkids.on.ca/app).…”