No abstract

The most common mutation of the cystic fibrosis transmembrane conductance regulator gene, CFTR, associated with the clinical disorder cystic fibrosis (CF) is called "APhe5N," a triple-base deletion resulting in loss of phenylalanine at residue 508 of the predicted 1480-amino acid CFTR CFTR gene expression quantified by limited polymerase chain reaction amplification showed that in normal individuals, CFTR mRNA transcripts are expressed in nasal, tracheal, and bronchial epithelial cells at -1-2 copies per cell, more than 100-fold greater than in pharyngeal epithelium. Importantly, allele-specific hybridization studies demonstrated that the normal and APhe5" CFTR alleles are expressed in the respiratory epithelium in similar amounts.Cystic fibrosis (CF) is a fatal recessive disorder caused by mutations of the CF transmembrane conductance regulator gene, CFTR, whose postulated protein product is a 1480-amino acid membrane protein thought to modulate Clsecretion across the apical membrane of epithelial cells (1-4). The most common mutation of the CFTR gene is called "Afe 508 ," a triple-base deletion resulting in loss of the codon for phenylalanine at residue 508 of the predicted protein sequence found on ;'"70% ofchromosomes containing an abnormal CFTR gene (3, 4). All organs with exocrine glands are affected by abnormalities of the CFTR gene, but the major clinical manifestations are in the respiratory tract, with impacted mucus, chronic infection, and inflammation with subsequent derangements of airways and lung parenchyma (1). It is not known how mutations in the CFTR gene cause the respiratory abnormalities, but it is assumed to be directly related to abnormalities in expression of the CFTR gene in the respiratory epithelium. As an approach to this question, the present study is directed toward quantifying in vivo CFTR gene expression at the mRNA level in respiratory epithelium of normals and individuals with CF. METHODS

Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects.

Background & Aims Cystic fibrosis liver disease (CFLD), a leading cause of death in cystic fibrosis (CF), is mostly described in pediatric populations. Adult-onset CFLD lacks sufficient characterization and diagnostic tools. Methods A cohort of CF patients without CFLD during childhood were followed for up to 38 years with serologic testing, imaging, and noninvasive fibrosis markers. Historical CFLD diagnostic criteria were compared with a newly proposed CFLD criteria. Results 36 CF patients were followed for a median of 24.5 years(IQR=15.6, 32.9). By the last follow-up, 11(31%) had died. With conventional criteria, 8(22%) patients had CFLD, and by new criterion, 17 (47%) had CFLD at a median age of 36.6 years(IQR=26.5, 43.2). By new criterion, those with CFLD had higher median ALT(42 vs 27, p=0.005), AST(26 vs 21, p=0.01), direct bilirubin(0.13 vs 0.1, p=0.01), PT(14.4 vs 12.4, p=0.002), and APRI(0.31 vs 0.23, p=0.003) over the last two years of follow-up. Subjects with a Fibroscan® >6.8kPa had higher ALT(42 vs 28U/L, p=0.02), AST(35 vs 25U/L, p=0.02), APRI(0.77 vs 0.25, p=0.0004), FIB-4(2.14 vs 0.74, p=0.0003) and lower platelet counts(205 vs 293, p=0.02). One CFLD patient had nodular regenerative hyperplasia. Longitudinally, mean platelet counts significantly declined in the CFLD group(310 to 230U/L, p=0.0005). Deceased CFLD patients had lower platelet counts than those alive with CFLD(143 vs 258 U/L, p=0.004) or those deceased with no CFLD(143 vs 327U/L, p=0.006). Conclusion Adult-onset CFLD may be more prevalent than previously described which suggests a later wave of CFLD that impacts morbidity. Routine liver tests, radiologic imaging, noninvasive fibrosis markers and fibroscan® can be utilized algorithmically to identify adult CFLD. Further evaluation in other CF cohorts should be performed for validation.