CFTR founder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis.
Mol Genet Genomic Med
; 5(1): 40-49, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-28116329
ABSTRACT
BACKGROUND:
Cystic fibrosis (CF) is a rare condition in Asians. Since 1985, only about 30 Chinese patients have been reported with molecular confirmation.METHOD:
Using our in-house next-generation sequencing (NGS) pipeline for childhood bronchiectasis, we identified disease-causing CFTR mutations 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 CFTRc.3068T>Gp.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.CONCLUSION:
Together with other previously reported mutations, the specific founder mutation presented herein suggests a unique CFTR mutation 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Mol Genet Genomic Med
Ano de publicação:
2017
Tipo de documento:
Article