Yuelin Shen1, Jinrong Liu1, Lili Zhong2, Peter J Mogayzel3, Pamela L Zeitlin3, Patrick R Sosnay4, Shunying Zhao5. 1. Department No. 2 of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, China. 2. Pediatric Institute, Hunan Provincial People's Hospital, Changsha, China. 3. Department of Pediatrics, Cystic Fibrosis Center, Johns Hopkins University School of Medicine, Baltimore, MD. 4. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD. 5. Department No. 2 of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, China. Electronic address: zhaoshunying2001@163.com.
Abstract
OBJECTIVES: To characterize the clinical phenotypes and genotypic spectrum of cystic fibrosis (CF) in Chinese children. STUDY DESIGN: We recruited and characterized the phenotypes of 21 Chinese children with CF. All 27 exons and their flanking sequences of the CF transmembrane conductance regulator gene were amplified and sequenced to define the genotypes. RESULTS: Bronchiectasis (95.2%) and sinusitis (76.2%) were the most common clinical presentations among our patients. By contrast, pancreatic insufficiency was rare (14.3%). The predominant organism found in the airways was Pseudomonas aeruginosa (66.7%). There were obvious reductions of forced expiratory volume in the first second (mean ± SD: 71.8% ± 17.2% predicted) and forced expiratory flows at 75% of exhaled vital capacity (33.7% ± 20.4% predicted) in children with CF. Overall, we identified 22 different mutations, including 12 missense, 5 nonsense, 2 frameshift, 1 in-frame insertion, 1 splice site, and 1 3'untranslated region mutation. Of these, 7 were novel observations (W216X[780G→A], 1092insA, Q359X, D567Y, 2623-126T→C, 3439delA and 4575+110C→G), and the most common types were L88X and I556V. One de novo mutation (1092insA) was also revealed. Except for N1303K and R334W, none of them were present in the common Caucasian CF transmembrane conductance regulator mutation-screening panels. CONCLUSIONS: There was a 5.7-year delay between the first clinical presentation and the eventual CF diagnosis, suggesting that CF may be underdiagnosed in China. The clinical phenotypes and genotypic spectrum are different from that observed in Caucasians.
OBJECTIVES: To characterize the clinical phenotypes and genotypic spectrum of cystic fibrosis (CF) in Chinese children. STUDY DESIGN: We recruited and characterized the phenotypes of 21 Chinese children with CF. All 27 exons and their flanking sequences of the CF transmembrane conductance regulator gene were amplified and sequenced to define the genotypes. RESULTS: Bronchiectasis (95.2%) and sinusitis (76.2%) were the most common clinical presentations among our patients. By contrast, pancreatic insufficiency was rare (14.3%). The predominant organism found in the airways was Pseudomonas aeruginosa (66.7%). There were obvious reductions of forced expiratory volume in the first second (mean ± SD: 71.8% ± 17.2% predicted) and forced expiratory flows at 75% of exhaled vital capacity (33.7% ± 20.4% predicted) in children with CF. Overall, we identified 22 different mutations, including 12 missense, 5 nonsense, 2 frameshift, 1 in-frame insertion, 1 splice site, and 1 3'untranslated region mutation. Of these, 7 were novel observations (W216X[780G→A], 1092insA, Q359X, D567Y, 2623-126T→C, 3439delA and 4575+110C→G), and the most common types were L88X and I556V. One de novo mutation (1092insA) was also revealed. Except for N1303K and R334W, none of them were present in the common Caucasian CF transmembrane conductance regulator mutation-screening panels. CONCLUSIONS: There was a 5.7-year delay between the first clinical presentation and the eventual CF diagnosis, suggesting that CF may be underdiagnosed in China. The clinical phenotypes and genotypic spectrum are different from that observed in Caucasians.
Authors: Scott C Bell; Marcus A Mall; Hector Gutierrez; Milan Macek; Susan Madge; Jane C Davies; Pierre-Régis Burgel; Elizabeth Tullis; Claudio Castaños; Carlo Castellani; Catherine A Byrnes; Fiona Cathcart; Sanjay H Chotirmall; Rebecca Cosgriff; Irmgard Eichler; Isabelle Fajac; Christopher H Goss; Pavel Drevinek; Philip M Farrell; Anna M Gravelle; Trudy Havermans; Nicole Mayer-Hamblett; Nataliya Kashirskaya; Eitan Kerem; Joseph L Mathew; Edward F McKone; Lutz Naehrlich; Samya Z Nasr; Gabriela R Oates; Ciaran O'Neill; Ulrike Pypops; Karen S Raraigh; Steven M Rowe; Kevin W Southern; Sheila Sivam; Anne L Stephenson; Marco Zampoli; Felix Ratjen Journal: Lancet Respir Med Date: 2019-09-27 Impact factor: 30.700