title: CFTRfounder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis.
abstract: BACKGROUND
  Cystic fibrosis (CF) is a rare condition in Asians. Since 1985, only about 30 Chinese patients have been reported with molecular confirmation.
  
  
  METHODS
  Using our in-house next-generation sequencing (NGS) pipeline for childhood bronchiectasis, we identified disease-causingCFTRmutations in CF patients in Hong Kong. After identifying p.I1023R in multiple patients, haplotype analysis was performed with genome-wide microarray to ascertain the likelihood of this being a founder mutation. We also assessed the processing and gating activity of the mutant protein by Western hybridization and patch-clamp test.
  
  
  RESULTS
  Molecular diagnoses were confirmed in four patients, three of whom shared a missense mutation:CFTR:c.3068T>G:p.I1023R. The results suggested that p.I1023R is a founder mutation in southern Han Chinese. In addition, the processing and gating activity of the mutant protein was assessed by gel electrophoresis and a patch-clamp test. The mutant protein exhibited trafficking defects, suggesting that the dysfunction is caused by reduced cell surface expression of the fully glycosylated proteins.
  
  
  CONCLUSIONS
  Together with other previously reported mutations, the specific founder mutation presented herein suggests a uniqueCFTRmutation spectrum in the southern Chinese populations, and this finding has vital implications for improving molecular testing and mutation-specific treatments for Chinese patients with CF.
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Gordon K C
authors.initials: GK
authors.lastname: Leung
authors.affiliation: Department of Psychiatry LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Dingge
authors.initials: D
authors.lastname: Ying
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Christopher C Y
authors.initials: CC
authors.lastname: Mak
authors.affiliation: HKU Shenzhen Institute of Research and Innovation School of Biomedical Sciences The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Chen
authors.affiliation: HKU Shenzhen Institute of Research and Innovation School of Biomedical Sciences The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Kit-San
authors.initials: KS
authors.lastname: Yeung
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Wai-Lap
authors.initials: WL
authors.lastname: Wong
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Yoyo W Y
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Gary T K
authors.initials: GT
authors.lastname: Mok
authors.affiliation: Department of Paediatrics and Adolescent Medicine Queen Mary Hospital Hong Kong Hong Kong.
authors.forename: Christy S K
authors.initials: CS
authors.lastname: Chau
authors.affiliation: NHS Lothian Lothian NHS Board Edinburgh UK.
authors.forename: Jenna
authors.initials: J
authors.lastname: McLuskey
authors.affiliation: Department of Genetics Kuala Lumpur Hospital Kuala Lumpur Malaysia.
authors.forename: Winnie P T
authors.initials: WP
authors.lastname: Ong
authors.affiliation: Department of Genetics Kuala Lumpur Hospital Kuala Lumpur Malaysia.
authors.forename: Huey-Yin
authors.initials: HY
authors.lastname: Leong
authors.affiliation: Department of Obstetrics and Gynaecology Tsan Yuk Hospital Hong Kong Hong Kong.
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.affiliation: Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.affiliation: HKU Shenzhen Institute of Research and Innovation School of Biomedical Sciences The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Jeng-Haur
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Paediatrics Faculty of Medicine The Chinese University of Hong Kong Hong Kong Hong Kong.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Li
authors.affiliation: Department of Psychiatry LKS Faculty of Medicine The University of Hong Kong Hong Kong Hong Kong.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Department of Paediatrics and Adolescent MedicineLKS Faculty of MedicineThe University of Hong KongHong KongHong Kong; Department of Paediatrics and Adolescent MedicineQueen Mary HospitalHong KongHong Kong.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Paediatrics and Adolescent MedicineLKS Faculty of MedicineThe University of Hong KongHong KongHong Kong; Department of Paediatrics and Adolescent MedicineQueen Mary HospitalHong KongHong Kong; Department of Paediatrics and Adolescent MedicineThe Duchess of Kent Children's Hospital at Sandy BayHong Kong.
authors.forename: Brian H Y
authors.initials: BH
authors.lastname: Chung
authors.affiliation: Department of Paediatrics and Adolescent MedicineLKS Faculty of MedicineThe University of Hong KongHong KongHong Kong; Department of Paediatrics and Adolescent MedicineQueen Mary HospitalHong KongHong Kong; Department of Paediatrics and Adolescent MedicineThe Duchess of Kent Children's Hospital at Sandy BayHong Kong.
authors.forename: So-Lun
authors.initials: SL
authors.lastname: Lee
keywords: Bronchiectasis; Chinese; cystic fibrosis; founder mutation; trafficking defects