Research Day
TWO SISTERS WITH A UNIQUE CFTR MUTATION, P.I1328T, RESULTING IN CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR-RELATED METABOLIC SYNDROME
Document Type
Abstract
Date
2021
Abstract
Background: Cystic Fibrosis (CF), a life-shortening, autosomal-recessive disease arises due to mutations in the CFTR gene, commonly leading to pulmonary and digestive symptoms. While numerous mutations have been proven to cause CF, there are an even larger number of CFTR mutations that have yet to be clinically described. Patients who are positive on newborn screening with elevated immunoreactive trypsinogen (IRT) and have a sweat chloride values <60 mmol/L or fewer than 2 disease-causing mutations in the CFTR gene, are given the designation of CFTR-related metabolic syndrome (CRMS). CRMS is a newer designation, to which the clinical implications have not yet been fully elucidated.
Case History: To our knowledge, the patients presented in this series represent the first documented case of CRMS siblings sharing the p.Ile1328Thr variant of CFTR. The sisters in this case were 24 months (Patient A) and 10 months (Patient B) of age, and had identical mutations in CFTR: the CF-causing p.Phe508del mutation, and the variant of uncertain significance p.I1328T. Patient A had an extensive medical and surgical history, due to her complicated renal pathology. Patient B suffered from stridor/laryngomalacia, adequately managed by medical intervention. Both sisters suffered from severe cases of gastroesophageal reflux disease (GERD).
Conclusions: This case series documents the symptoms observed in two individuals with the p.I1328T mutation, which has only been previously observed in 2 individuals, neither of whom developed CF. Due to the benefits of early intervention for CF patients, monitoring of CRMS patients is essential to ensuring optimal patient outcomes.