Heterogeneous Spectrum of CFTR Gene Mutations in Korean Patients with Cystic Fibrosis
2
조회
0
다운로드
7
인용
0
참고문헌
키워드
초록
Background: Cystic 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. Methods: In 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. Results: Three 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. Conclusions: Sequencing 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.
Abstract
Background: Cystic 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. Methods: In 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. Results: Three 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. Conclusions: Sequencing 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.
참고문헌 (33)
- Welsh MJ, "Gene transfer for cystic fibrosis", J Clin Invest, 104, pp.1165~1166 (1999)
- Behrman R, "Nelson textbook of pediatrics. 17th ed" (2004), Saunders
- Kerem B, "Identification of the cystic fibrosis gene: genetic analysis", Science, 245, pp.1073~1080 (1989)
- Riordan JR, "Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA", Science, 245, pp.1066~1073 (1989)
- Zielenski J, "Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene", Genomics, 10, pp.214~228 (1991)
- Bear CE, "Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR)", Cell, 68, pp.809~818 (1992)
- FitzSimmons SC, "The changing epidemiology of cystic fibrosis", Curr Probl Pediatr, 24, pp.171~179 (1994)
- Collins FS, "Cystic fibrosis: molecular biology and therapeutic implications", Science, 256, pp.774~779 (1992)
- ECFTN, "The molecular genetic epidemiology of cystic fibrosis. Report of a joint meeting of WHO", pp.World Health Organization, ICF (M)A
- Imaizumi Y, "Incidence and mortality rates of cystic fibrosis in Japan, 1969-1992", Am J Med Genet, 58, pp.161~168 (1995)
- Yamashiro Y, "The estimated incidence of cystic fibrosis in Japan", J Pediatr Gastroenterol Nutr, 24, pp.544~547 (1997)
- Moon HR, "Cystic fibrosis--a case presented with recurrent bronchiolitis in infancy in a Korean male infant", J Korean Med Sci, 3, pp.157~162 (1988)
- 박시현, "낭성 섬유증: 증례 보고", 대한영상의학회지, 47(6), pp.693~696 (2002), 대한영상의학회
- Ahn KM, "Cystic Fibrosis in Korean Children:A Case Report Identified by a Quantitative Pilocarpine Iontophoresis Sweat Test and Genetic Analysis", Journal of Korean Medical Science, 20(1), pp.153~ (2005), 대한의학회
- Won Jung Koh, "Report of a Korean Patient with Cystic Fibrosis, Carrying Q98R and Q220X Mutations in the CFTR Gene", Journal of Korean Medical Science, 21(3), pp.563~566 (2006), 대한의학회
- 황인옥, "A case of cystic fibrosis presented with meconium ileus in a female neonate", Korean Journal of Pediatrics, 50(12), pp.1252~1256 (2007), 대한소아과학회
- 김수정, "한국인 낭성 섬유증 진단을 위한 표준화된 땀 유발 염소 농도 분석", Annals of Laboratory Medicine, 28(4), pp.274~281 (2008), 대한진단검사의학회
- 최영준, "Novel CFTR Mutations in a Korean Infant with Cystic Fibrosis and Pancreatic Insufficiency", Journal of Korean Medical Science, 25(1), pp.163~165 (2010), 대한의학회
- 지헌영, "The L441P Mutation of Cystic Fibrosis Transmembrane conductance Regulator and its Molecular Pathogenic Mechanisms in a Korean Patient with Cystic Fibrosis", Journal of Korean Medical Science, 25(1), pp.166~171 (2010), 대한의학회
- "Cystic Fibrosis Mutation Database"[URL]
- Tsui LC, "The cystic fibrosis transmembrane conductance regulator gene", Am J Respir Crit Care Med, 151, pp.47~53 (1995)
- Bowler IM, "Cystic fibrosis in Asians", Arch Dis Child, 68, pp.120~122 (1993)
- Kabra M, "Is the spectrum of mutations in Indian patients with cystic fibrosis different", Am J Med Genet, 93, pp.161~163 (2000)
- Powers CA, "Cystic fibrosis in Asian Indians", Arch Pediatr Adolesc Med, 150, pp.554~555 (1996)
- Sharma N, "Identification and characterization of CFTR gene mutations in Indian CF patients", Ann Hum Genet, 73, pp.26~33 (2009)
- Shah U, "Cystic fibrosis: defining a disease under-diagnosed in Pakistan", Trop Med Int Health, 14, pp.542~545 (2009)
- Alibakhshi R, "Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations", J Cyst Fibros, 7, pp.102~109 (2008)
- Schouten JP, "Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification", Nucleic Acids Res, 30, pp.57~ (2002)
- 고정민, "Identification of a Novel Mutation of CFTR Gene in a Korean Patient with Cystic Fibrosis", Journal of Korean Medical Science, 23(5), pp.912~915 (2008), 대한의학회
- Strom CM, "Extensive sequencing of the cystic fibrosis transmembrane regulator gene: assay validation and unexpected benefits of developing a comprehensive test", Genet Med, 5, pp.9~14 (2003)
- Gilljam M, "Clinical manifestations of cystic fibrosis among patients with diagnosis in adulthood", Chest, 126, pp.1215~1224 (2004)
- Yankaskas JR, "Cystic fibrosis adult care: consensus conference report", Chest, 125(1), pp.1~39 (2004)
- Kilinc MO, "Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients", Am J Med Genet, 113, pp.250~257 (2002)