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F1099L-CFTR (c.3297C>G) has Impaired Channel Function and Associates with Mild Disease Phenotypes in Two Pediatric Patients.

ABSTRACT: (1) Background: many rare cystic fibrosistransmembrane conductance regulator (CFTR) mutations remain poorly characterized with regard to functional consequences of the mutation. We present the clinical features of two pediatric cystic fibrosis (CF) subjects who are heterozygous for F1099L (c.3297C>G), one with G551D (a class III mutation) and one with 3849 + 10kbC->T (a class V mutation). We also identified the molecular defect(s) that are associated with F1099L mutation to correlate with the clinical features that we observed; (2) Methods: clinical findings and history were extracted from the electronic medical record and de-identified. F1099L-CFTR protein expression level and maturation status, channel function, and the effects of CFTR modulation on these characteristics were investigated using western blotting and iodide efflux assay; (3) Results: these two subjects have mild CF phenotypes when F1099L is combined with two known disease-causing mutations. F1099L-CFTR has a moderate defect in processing and maturation, causing fewer CFTR channels at the cell surface and, therefore, impaired channel activities. These defects could be effectively corrected using VX-809 (lumacaftor); and, (4) Conclusions: our biochemical data correlate with the disease manifestations and suggest that F1099L is potentially a CF-causing mutation. The study expands our knowledge of rare CFTR mutations and may help in developing effective therapies for subjects with F1099L mutation.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7915716 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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F1099L-CFTR (c.3297C>G) has Impaired Channel Function and Associates with Mild Disease Phenotypes in Two Pediatric Patients.

Zhang Xiaoying X Hothi Jaspal S JS Zhang Yanhui H YH Ren Aixia A Rock Michael J MJ Srinivasan Saumini S Stokes Dennis C DC Naren Anjaparavanda P AP Zhang Weiqiang W

Life (Basel, Switzerland) 20210208 2

(1) Background: many rare <i>cystic fibrosis</i><i>transmembrane conductance regulator</i> (CFTR) mutations remain poorly characterized with regard to functional consequences of the mutation. We present the clinical features of two pediatric cystic fibrosis (CF) subjects who are heterozygous for F1099L (c.3297C>G), one with G551D (a class III mutation) and one with 3849 + 10kbC->T (a class V mutation). We also identified the molecular defect(s) that are associated with F1099L mutation to correla ...[more]

PMID: 33567498

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Project description:The purpose of this article is to investigate the spectrum of physical function of pediatric liver transplantation (LT) recipients 12-24 months after LT. Review data were collected through the functional outcomes group, an ancillary study of the Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12-24 months. Children???8 years and parents completed the Pediatric Quality of Life Inventory™ 4.0 generic core scales, which includes 8 questions assessing physical function. Scores were compared to a matched healthy child population (n?=?1658) and between survivors with optimal versus nonoptimal health. A total of 263 patients were included. Median age at transplant and survey was 4.8 years (interquartile range [IQR], 1.3-11.4 years) and 5.9 years (IQR, 2.6-13.1 years), respectively. The mean physical functioning score on child and parent reports were 81.2?±?17.3 and 77.1?±?23.7, respectively. Compared to a matched healthy population, transplant survivors and their parents reported lower physical function scores (P?<?0.001); 32.9% of patients and 35.0% of parents reported a physical function score <75, which is?>?1 standard deviation below the mean of a healthy population. Physical functioning scores were significantly higher in survivors with optimal health than those with nonoptimal health (P?<?0.01). There was a significant relationship between emotional functioning and physical functioning scores for LT recipients (r?=?0.69; P?<?0.001). In multivariate analysis, primary disease, height z score?<?-1.64 at longterm follow-up (LTF) visit, ?>?4 days of hospitalization since LTF visit, and not being listed as status 1 were predictors of poor physical function. In conclusion, pediatric LT recipients 1-2 years after LT and their parents report lower physical function than a healthy population. Findings suggest practitioners need to routinely assess physical function, and the development of rehabilitation programs may be important.

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F1099L-CFTR (c.3297C>G) has Impaired Channel Function and Associates with Mild Disease Phenotypes in Two Pediatric Patients.

Publications

F1099L-CFTR (c.3297C>G) has Impaired Channel Function and Associates with Mild Disease Phenotypes in Two Pediatric Patients.

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