Abstract Objective To study the clinical features and gene mutation sites of children with cystic fibrosis (CF), in order to improve the understanding of CF to reduce misdiagnosis and missed diagnosis. Methods A retrospective analysis was performed on the medical records of 8 children with CF who were diagnosed in Hebei Children's Hospital from 2018 to 2021. Results Among the 8 children with CF, there were 5 boys and 3 girls, with an age of 3-48 months (median 8 months) at diagnosis, and the age of onset ranged from 0 to 24 months (median 2.5 months). Clinical manifestations included recurrent respiratory infection in 7 children, sinusitis in 3 children, bronchiectasis in 4 children, diarrhea in 8 children, fatty diarrhea in 3 children, suspected pancreatic insufficiency in 6 children, pancreatic cystic fibrosis in 1 child, malnutrition in 5 children, and pseudo-Bartter syndrome in 4 children. The most common respiratory pathogens were Pseudomonas aeruginosa (4 children). A total of 16 mutation sites were identified by high-throughput sequencing, multiplex ligation-dependent probe amplification, and Sanger sequencing, including 5 frameshift mutations, 4 nonsense mutations, 4 missense mutations, 2 exon deletions, and 1 splice mutation. CFTR mutations were found in all 8 children. p.G970D was the most common mutation (3 children), and F508del mutation was observed in one child. Four novel mutations were noted: deletion exon15, c.3796_3797dupGA(p.I1267Kfs*12), c.2328dupA(p.V777Sfs*2), and c.2950G>A(p.D984N). Conclusions p.G970D is the most common mutation type in children with CF. CF should be considered for children who have recurrent respiratory infection or test positive for Pseudomonas aeruginosa, with or without digestive manifestations or pseudo-Bartter syndrome.
Corresponding Authors:
Liu J-H，E-mail：liuwjm@sina.com
E-mail: liuwjm@sina.com
Cite this article:
ZHANG Na,LIU Jian-Hua,CHU Ya-Juan et al. Clinical and gene mutation features of cystic fibrosis: an analysis of 8 cases[J]. CJCP, 2022, 24(7): 771-777.
ZHANG Na,LIU Jian-Hua,CHU Ya-Juan et al. Clinical and gene mutation features of cystic fibrosis: an analysis of 8 cases[J]. CJCP, 2022, 24(7): 771-777.
3 Cystic Fibrosis Trust. UK cystic fibrosis registry annual data report 2019[EB/OL]. [2021-10-20]. https://www.cysticfibrosis.org.uk/sites/default/files/2020-12/2019%20Registry%20Annual%20Data%20report_Sep%202020.pdf.
Izumikawa K, Tomiyama Y, Ishimoto H, et al. Unique mutations of the cystic fibrosis transmembrane conductance regulator gene of three cases of cystic fibrosis in Nagasaki, Japan[J]. Intern Med, 2009, 48(15): 1327-1331. PMID: 19652440. DOI: 10.2169/internalmedicine.48.2078.
Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the cystic fibrosis foundation[J]. J Pediatr, 2017, 181S: S4-S15.e1. PMID: 28129811. DOI: 10.1016/j.jpeds.2016.09.064.
Shen Y, Tang X, Liu J, et al. Pseudo-Bartter syndrome in Chinese children with cystic fibrosis: clinical features and genotypic findings[J]. Pediatr Pulmonol, 2020, 55(11): 3021-3029. PMID: 32761997. DOI: 10.1002/ppul.25012.
Mantoo MR, Kabra M, Kabra SK. Cystic fibrosis presenting as Pseudo-Bartter syndrome: an important diagnosis that is missed![J]. Indian J Pediatr, 2020, 87(9): 726-732. PMID: 32504456. DOI: 10.1007/s12098-020-03342-8.
Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic fibrosis foundation pulmonary guideline. pharmacologic approaches to prevention and eradication of initial Pseudomonas aeruginosa infection[J]. Ann Am Thorac Soc, 2014, 11(10): 1640-1650. PMID: 25549030. DOI: 10.1513/AnnalsATS.201404-166OC.
Shi R, Wang X, Lu X, et al. A systematic review of the clinical and genetic characteristics of Chinese patients with cystic fibrosis[J]. Pediatr Pulmonol, 2020, 55(11): 3005-3011. PMID: 32716133. DOI: 10.1002/ppul.24980.
Grody WW, Cutting GR, Klinger KW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening[J]. Genet Med, 2001, 3(2): 149-154. PMID: 11280952. DOI: 10.1097/00125817-200103000-00010.
28 Marshall B, Faro A, Elbert A, et al. 2018 patient registry annual data report[EB/OL]. [2021-10-20]. https://www.cff.org/medical-professionals/patient-registry.
LIANG Wei-Ling, YE Xiao-Fan, ZHONG Gong, CHEN Jian-Jun, DAI Kang-Lin, CHEUK Ka Leung Daniel, MO Shu, WANG Bo-Shen, LI Chun-Yu, JIANG Xuan-Zhu, XU Zhi-Yuan, ZHOU Li, CHAN Irene, CHEN Jian-Liang, CHU Patrick., LEE Pui Wah Pamela, CHAN Chi Fung Godfrey. Clinical efficacy of combined therapy in children with stage 4 neuroblastoma[J]. CJCP, 2022, 24(7): 759-764.
Shaanxi Province Diagnosis and Treatment Center of Kawasaki Disease/Children's Hospital of Shaanxi ProvincialPeople's Hospital, Children's Hospital of Shanghai Jiao Tong University, Beijing Children's Hospital of Capital MedicalUniversity, Shengjing Hospital of China Medical University, Affiliated Hospital of Yan'an University, Expert Committeeof Advanced Training for Pediatrician, China Maternal and Children's Health Association, General Pediatric Group ofPediatrician Branch of Chinese Medical Doctor Association, Pediatric International Exchange and Cooperation Center,Shanghai Cooperation Organization Hospital Cooperation Alliance, Editorial Board of Chinese Journal ofContemporary Pediatrics. Pediatric expert consensus on the application of aspirin in Kawasaki disease[J]. CJCP, 2022, 24(6): 597-603.
