Cystic Fibrosis (CF) is a rare condition among Asians and has not been reported in the Philippines as of this time. The inclusion of this disease in the Philippines’ Expanded Newborn Screening Program (ENBS) has provided this Filipino family the opportunity of early detection and appropriate management of this condition that could ensure the survival of the proband and his other surviving siblings. Here we present a case of a 24-month-old male who had a positive Expanded Newborn Screening (ENBS) test for cystic fibrosis and eventually underwent further tests to confirm a homozygous deletion of exons 1 - 2 of the CFTR gene. He subsequently had recurrent pneumonia but is being managed by a team consisting of a pulmonologist, gastroenterologist, and a metabolic dietitian. The proband had an older sibling whose Newborn Screening (NBS) test was normal and who eventually expired from recurrent bouts of pneumonia. This sibling was never managed as a case of cystic fibrosis. Implications on the diagnosis and management of CF in the local setting is also discussed. The importance of an appropriate CF panel customized to the local population should be reiterated and carrier testing should be encouraged to help with proper family counseling for future pregnancies for the family involved.
Cystic Fibrosis ; Neonatal Screening ; Philippines

The frequency of diagnosing bronchiectasis is increasing around the world. Cystic fibrosis is the most common inherited cause of bronchiectasis, but there is increasing recognition of significant numbers of patients with bronchiectasis from various causes. With increasing awareness of bronchiectasis, a significant number of research, concerning the causes and treatments, were published over the past few years. Investigation of the underlying cause of bronchiectasis is the most important key to effective management. The purpose of this report is to review the immunological abnormalities that cause bronchiectasis in those that the cystic fibrosis has been excluded, identify the available evidences of current management, and discuss several controversies in the treatment of this disorder.
Bronchiectasis ; Cystic Fibrosis ; Humans ; Immunologic Deficiency Syndromes

BACKGROUND AND OBJECTIVES: Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel protein that plays an important role in electrolyte and water transport, whose kinetics and localization are altered in cystic fibrosis (CF). Previous studies showed its presence in the apical domain of ciliated respiratory epithelial cells, and airway secretory glands. The purpose of this study was to characterize the localization of CFTR in the epithelium of nasal polyp of the subjects without phenotypic expression of cystic fibrosis. MAERIALS AND METHODS: Immunohistochemical staining for CFTR, using monoclonal mouse anti-human CFTR, were performed on tissue sections of 4 normal turbinate and nasal polyps from 10 patients who underwent intranasal operation. RESULTS: The nasal polyp epithelium demonstrated a heterogeneous pattern of CFTR expressions, including diffuse or scattered cytoplasmic labeling, very low to undetectable labeling, intense perinuclear staining, and typical apical location. CONCLUSION: These results suggest that abnormal expression and distribution of the CFTR may have a role in the formation of nasal polyp.
Animals ; Chloride Channels ; Cystic Fibrosis Transmembrane Conductance Regulator* ; Cystic Fibrosis* ; Cytoplasm ; Epithelial Cells* ; Epithelium ; Humans ; Kinetics ; Mice ; Nasal Polyps* ; Turbinates

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
China ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Humans ; Mutation ; Poly T ; RNA, Messenger/genetics*

BACKGROUND: Cystic fibrosis (CF) is one of the most common hereditary disorders among Caucasians. The most common mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been well established among Caucasian populations. In Koreans, however, there are very few cases of genetically confirmed CF thus far, and the spectrum of mutations seems quite different from that observed in Caucasians. METHODS: In the present study, we describe the cases of 2 Korean CF patients, present sequencing results identifying mutations in their CFTR gene, and summarize the results of CFTR mutational spectrum from previously reported Korean CF patients. The mutations described were identified by performing direct sequencing analysis of the complete coding regions and flanking intronic sequences of the CFTR gene, followed by multiplex ligation-dependent probe amplification (MLPA) analysis in order to detect gene deletions or duplications that could not be identified by a direct sequencing method. RESULTS: Three CFTR mutations were identified in the 2 patients, including p.Q98R, c.2052delA, and c.579+5G>A. In an analysis of 9 Korean CF patients that included the 2 patients presented in this study, p.Q98R mutation was the only recurrently observed mutation with a frequency of 18.8% (3/16 alleles). Furthermore, only one of the mutations (c.3272-26A>G) was found among the 32 common mutations in the screening panel for Caucasians from the Cystic Fibrosis Mutation Database. CONCLUSIONS: Sequencing of the entire CFTR gene followed by MLPA analysis, rather than using the targeted sequencing-based screening panel for mutations commonly found in Caucasian populations, is recommended for genetic analysis of Korean CF patients.
Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Cystic Fibrosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Republic of Korea ; Sequence Analysis, DNA ; Young Adult

Cystic fibrosis is the most common autosomal recessive disease in Caucasian. Cystic fibrosis is caused by cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations that lead to dysfunction of chloride ion channel regulations in the epithelium. Cystic fibrosis can affect multiple organ functions, resulting in various signs and symptoms. Typically, chronic airway infection, maldigestion, failure to thrive, and male infertility can occur. There are approximately 1800 CFTR gene mutations which have been identified thus far. However, there are only a few types of mutations reported in Korea because the prevalence of the disease is different among ethnicitiess and nations. Despite its rarity, reports of CFTR mutations or diagnosed patients on the rise. Therefore, we have to detect better outcomes as early as possible based on a precise understanding of the disease entity. We report a 9-year-old girl carrying D339Y and Q220X gene mutations, as the first case report of a D339Y mutation in Korea.
Child ; Chloride Channels ; Cystic Fibrosis ; Cystic Fibrosis Transmembrane Conductance Regulator ; Epithelium ; Failure to Thrive ; Humans ; Infertility, Male ; Korea ; Lifting ; Male ; Prevalence ; Social Control, Formal

Although cystic fibrosis (CF) is one of the most frequently seen autosomal-recessive disorders in Caucasians, it is extremely rare in the Korean population. Recently, a 15-yr-old Korean boy was admitted to our hospital complaining of coughing, sputum, and exertional dyspnea. Chest radiographs and computed tomographic chest and paranasal sinus scans revealed diffuse bronchiectasis and pansinusitis. Pulmonary function tests revealed severe obstructive impairment. The average sweat chloride concentrations on both of the patients' forearms were 63.0 mM/L (reference limit: < 40 mM/L). Upon mutation analysis, two different mutations (Q98R and Q220X) were identified in the cystic fibrosis transmembrane conductance regulator gene, both of which had been previously detected in CF patients, one from France and the other from England. As CF is quite rare in Korea, the diagnosis of CF in this patient might be delayed. Therefore, we recommend that a diagnosis of CF should be suspected in patients exhibiting unexplained chronic respiratory symptoms.
Radiography, Thoracic ; Pedigree ; *Mutation ; Male ; Korea ; Humans ; Heterozygote ; *Genetic Predisposition to Disease ; Female ; DNA Mutational Analysis ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Cystic Fibrosis/*genetics ; Adolescent

BACKGROUND AND OBJECTIVES: Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel protein, its kinetics and localization are altered in cystic fibrosis. The purpose of this study was to evaluate whether the nasal polyp patients without phenotypic manifestation of cystic fibrosis have any form of CFTR mutations and to characterize the localization of CFTR in the nasal polyp. MATERIALS AND METHODS: The study group consisted of 71 subjects with nasal polyp who underwent an intranasal operation, and 20 normal subjects. Peripheral blood of the study groups were screened for mutation on the exon 3, 4, and 7 of the CFTR gene using single-stranded DNA conformational polymorphism (SSCP). Immunohistochemical staining for CFTR was conducted on the nasal polyps of studied subjects and normal turbinates as the control. RESULTS: While in the nasal polyp group, SSCP screening revealed two cases of mutant band on the exon 3, the normal control group did not show mutant band in all exons screened. CFTR showed the typical apical distribution in the normal turbinate mucosa, whereas in the nasal polyp, regardless of an abnormal band in exon 3, CFTR demonstrated a heterogenous pattern of localization consisting of cytoplasmic labeling, perinuclear staining, and intermingled apical location. CONCLUSION: These results suggest that an altered localization of the CFTR in the nasal polyps, based not only on the CFTR mutation but also on the acquired inflammatory process, may have an important role in the formation of nasal polyps.
Chloride Channels ; Cystic Fibrosis Transmembrane Conductance Regulator* ; Cystic Fibrosis* ; Cytoplasm ; DNA, Single-Stranded ; Exons ; Humans ; Immunohistochemistry ; Kinetics ; Mass Screening ; Mucous Membrane ; Nasal Polyps* ; Polymorphism, Single-Stranded Conformational ; Turbinates

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in Caucasians, but rare in Asians. The mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for CF. To date, less than 5 cases of CF have been reported and a few of them diagnosed based on the genotype of the CFTR gene in Korea. We encountered a 4-month-old Korean infant with CF and the diagnosis was confirmed by CFTR gene mutation analysis. The patient underwent surgical operation, due to meconium ileus at birth. He suffered by recurrent respiratory infections, failure to thrive, fatty liver with hepatomegaly, and cholestasis. The mutations of the CFTR gene were identified in the patient and his parents. The patient was a compound heterozygote with a nonsense mutation of c.263T>G, resulting in an amino acid change of p.Leu88X in exon 3. It was previously described in a Korean patient with CF. The other is a novel mutation; c.2089-2090insA mutation (p.Arg697LysfsX33) in exon 13. The mutation c.263T>G was inherited from his father, and the c.2089-2090insA mutation from his mother. Respiratory infection was recovered by supportive care, and cholestasis was improved slowly with sufficient feeding and supplementation of pancreatic exocrine enzymes. He is 19- month old now and shows catch-up growth. We report a novel CFTR mutation in a Korean infant with CF.
Alleles ; Base Sequence ; Cholestasis ; Cystic Fibrosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Infant ; Korea ; Male ; Molecular Sequence Data ; *Mutation ; Treatment Outcome

Cystic fibrosis (CF) of the pancreas is the most widely accepted name of the most common fatal inherited single gene defect disease among Caucasians. Its incidence among other races is thought to be significantly less, but mutations in the gene have been reported in most, if not all, major populations. This review is intended to give general concepts of the molecular as well as physiological basis of the pathology that develops in the disease. First, an overview of the organ pathology and genetics is presented, followed by the molecular structure of the gene product (cystic fibrosis transmembrane conductance regulator, CFTR), its properties, functions, and controls as currently understood. Second, since mutations appear to be expressed primarily as a defect in electrolyte transport, effects and mechanisms of pathology are presented for two characteristically affected organs where the etiology is best described: the sweat gland, which excretes far too much NaCl ("salt") and the pancreas, which excretes far too little HCO3(- )("soda"). Unfortunately, morbidity and mortality in CF develop principally from refractory airway infections, the basis of which remains controversial. Consequently, we conclude by considering possible mechanisms by which defects in anion transport might predispose the CF lung to chronic infections.
Anions ; metabolism ; Bicarbonates ; Cystic Fibrosis ; physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator ; metabolism ; Humans ; Ion Transport ; Pancreas ; physiopathology ; Sodium Chloride ; Sweat Glands ; physiopathology