Heterogeneous Spectrum of CFTR Gene Mutations in Korean Patients with Cystic Fibrosis

Abstract

BackgroundCystic fibrosis (CF) is one of the most common hereditary disorders among Caucasians. The most common mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been well established among Caucasian populations. In Koreans, however, there are very few cases of genetically confirmed CF thus far, and the spectrum of mutations seems quite different from that observed in Caucasians.MethodsIn the present study, we describe the cases of 2 Korean CF patients, present sequencing results identifying mutations in their CFTR gene, and summarize the results of CFTR mutational spectrum from previously reported Korean CF patients. The mutations described were identified by performing direct sequencing analysis of the complete coding regions and flanking intronic sequences of the CFTR gene, followed by multiplex ligation-dependent probe amplification (MLPA) analysis in order to detect gene deletions or duplications that could not be identified by a direct sequencing method.ResultsThree CFTR mutations were identified in the 2 patients, including p.Q98R, c.2052delA, and c.579+5G>A. In an analysis of 9 Korean CF patients that included the 2 patients presented in this study, p.Q98R mutation was the only recurrently observed mutation with a frequency of 18.8% (3/16 alleles). Furthermore, only one of the mutations (c.3272-26A>G) was found among the 32 common mutations in the screening panel for Caucasians from the Cystic Fibrosis Mutation Database.ConclusionsSequencing of the entire CFTR gene followed by MLPA analysis, rather than using the targeted sequencing-based screening panel for mutations commonly found in Caucasian populations, is recommended for genetic analysis of Korean CF patients.

Characterization of gene mutations and phenotypes of cystic fibrosis in Chinese patients

“…In the present study, the most common mutation in Caucasians, F508del, was not detected; R553X, a much less common mutation accounting for 0.7% of CF patients in Caucasians, was present in patient 2. Q98R is a mutation that was first reported in Southern France and is primarily detected in Koreans and Japanese, with a detection rate as high as 18.8% . This mutation was detected in two of our Chinese patients; one a homozygote born of consanguineous parents and the other a heterozygote.…”

“…Q98R is a mutation that was first reported in Southern France 21 and is primarily detected in Koreans and Japanese, with a detection rate as high as 18.8%. 22 This mutation was detected in two of our Chinese patients; one a homozygote born of consanguineous parents and the other a heterozygote. The rest of the mutations identified in the present study, are only reported in a few studies and mostly specific to Asians, as documented in HGMD.…”

Chest CT Features of Cystic Fibrosis in Korea: Comparison with Non-Cystic Fibrosis Diseases

“…In order to study the spectrum of CF in Korean patients, we reviewed the previously identified cases of CF at our institution (n = 5) (3818) and in the literature (n = 7) (4567919), in addition to the cases analyzed in this study (n = 2). Clinical and radiologic features of these patients were summarized in Table 2.…”

Differences in gene mutations between Chinese and Caucasian cystic fibrosis patients

“…Cystic fibrosis is the most frequently occurring life‐limiting autosomal recessive disorder among Caucasians populations, with a carrier frequency of about 1:25, resulting in a disease incidence of 1 in 2,500 live births . However, CF is quite rare in Asian populations, and an epidemiological study of the Japanese population found the incidence of CF to be about 1 in 350,000 . In China, there are no epidemiological statistics in incidence of this disease.…”

“…1 However, CF is quite rare in Asian populations, and an epidemiological study of the Japanese population found the incidence of CF to be about 1 in 350,000. 2 In China, there are no epidemiological statistics in incidence of this disease. There have been only 36 cases report from 1974 until the present.…”