Cystic fibrosis screening

Muller F, Dommergues M, Simon-Bouy B, Ferec C, Oury JF, Aubry MC, et al. Cystic fibrosis screening a fetus with hyperechogenic bowel may be the index case. 1 Med Genet 1998 35 657 -60. 

Strom CM, Huang D, Buller A, Redman J, Crossley B, Anderson B, et al. Cystic fibrosis screening using the College panel platform comparison and lessons learned from the first 20,000 samples. Genet Med 2002 4 289-96. 

To date, outside of dental matters considered later, the main ion-selective electrode interest on saliva has been the use of sodium glass electrodes for monitoring sodium levels in connection with cystic fibrosis screening, the high sodium content of parotid saliva being one characteristic of the disease [249, 250]. 

Within the biomedical field, the application of chloride ion-selective electrodes has largely been devoted to sweat analysis in relation to cystic fibrosis screening and diagnosis [159,251—271]. The disease, in which there is a malfunction of exocrine glands, can be readily diagnosed from the elevated chloride ion levels in patients sweat ( 100 mmol dm" ) compared with a normal ( 25 mmol dm ). Reasonably accurate monitoring of newborns, infants and children may... 

Specific ion electrodes, similar in design to the glass electrode, have been developed to analyze for a variety of cations and anions. One of the first to be used extensively was a fluoride ion electrode that is sensitive to F- at concentrations as low as 0.1 part per million and hence is ideal for monitoring fluoridated water supplies. An electrode that is specific for Cl- ions is used to diagnose cystic fibrosis. Attached directly to the skin, it detects the abnormally high concentrations of sodium chloride in sweat that are a characteristic symptom of this disorder. Diagnoses that used to require an hour or more can now be carried out in a few minutes as a result, large numbers of children can be screened rapidly and routinely. 

In addition to blood, certain types of specimens are submitted to the Pediatric laboratory which would not be commonly seen elsewhere. An example of this is sweat for analysis of chloride. The process of obtaining the sweat by iontophoresis usually falls to the personnel of the Laboratory of Neonatology (17). Stool for analysis of lipids and trypsin is more commonly submitted to the Laboratory of Neonatology than to the laboratory which services the adult population. The reason for this is that one is screening for certain intestinal diseases characteristic of infants and newborns which are rare in adults. Such conditions would be celiac disease, cystic fibrosis and others. 

Cystic fibrosis (CF) is the most common potentially lethal autosomal recessive disease among Caucasians. The incidence is estimated to be approximately 1 in 2000 births (Bl). Since it is inherited as an autosomal recessive condition, screening to identify couples at risk has been suggested. However, CF screening is complicated because many mutations of the CF gene exist. Thus, the feasibility of screening a population for carriers of cystic fibrosis gene mutations is primarily dependent upon the frequency of the common mutation in that population. 

Individuals with a family history of an autosomal or X-linked recessive disease may wish to know whether they are a heterozygous carrier of the disease. This can be established by genetic diagnosis (e.g., for cystic fibrosis, hemochromatosis, PKU, or albinism). In some specific cases, a population at high risk for a specific disease may be screened for carrier status using genetic diagnosis (e.g., Tay-Sachs disease in the Jewish population [see Clinical Correlate]). 

Chloride ion-selective electrodes The most important region of application is the determination of chlorides in waters, including sea water (for a review, see [167]), in serum [110,112,371] (review in [167]) and in soil [151,219,341], The determination of chloride ions in sweat made screening for cystic fibrosis possible in new-born babies (review, [45,55a, 262]). Br , I and S " interfere in the determination of chlorides in phosphate rocks [81]. Sulphite can be determined directly using an electrode with an Hgj CI2 - HgS membrane [398] on the basis of the reaction... 

T. Bray, G. C. F. Clark, G. J. Moody and J. D. R. Thomas, A Perspective of Sodium and Chloride Ion-Selective Electrode Sweat Tests for Screening in Cystic Fibrosis, University of Wales, Cardiff (1975). 

A study of an extended family in Venezuela with Huntington s chorea demonstrated that family members with the disease show a distinct and characteristic pattern of restriction fragment lengths, leading to a new screening test. The same methods of investigation revealed patterns for cystic fibrosis, adult polycystic kidney disease, Due lien nc muscular dystrophy, and others. 

Robertson NH, Weston SL, Kelly SJ, Duxbury NJ, Pearce SR, Elsmore P, Webb MBT, Newton CR, Little S. Development and validation of a screening test for 12 common mutations of the cystic fibrosis CFTR gene. Eur Respir J 1998 12 477-482. 

Cystic fibrosis is a lethal autosomal recessive disorder in Caucasians, with an incidence of 1 2000 in the general population. Newborn babies with this disease have increased serum trypsin concentrations. Thus, Crossley et al. developed a radioimmunoassay for human trypsin in dried blood samples on filter paper and used it for neonatal screening for this disease (C9). A non-isotopic immunoassay, such as enzyme immunoassay of trypsin, will be developed for this purpose. 

C9. Crossley, J. R., Smith, P. A., Edgar, B. W., Gluckman, P. D., and Elliott, R. B., Neonatal screening for cystic fibrosis, using immunoreactive trypsin assay in dried blood spots. Clin. Chim. Acta 113, 111-121 (1981). 

Parad, R. B., et al. (2005), Sweat testing infants detected by cystic fibrosis newborn screening, J. Pediatr., 147(3, Suppl), S69-72. 

L. J. V. Galietta, A. S. Verkman, High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening, /. Biol. Chem. 2002, 277, 37235-37241. 

Davies, K. (1992). Genetic screening for cystic fibrosis. Nature 357,425. 

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