Clinical Chemistry Siemens Point of Care - Urinalysis
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 45: 957-962, 1999;
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (16)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Castaldo, G.
Right arrow Articles by Salvatore, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Castaldo, G.
Right arrow Articles by Salvatore, F.
Related Collections
Right arrow Molecular Diagnostics and Genetics
Right arrow Pediatric Clinical Chemistry
Right arrow Automation and Analytical Techniques
(Clinical Chemistry. 1999;45:957-962.)
© 1999 American Association for Clinical Chemistry, Inc.

Articles

Detection of Five Rare Cystic Fibrosis Mutations Peculiar to Southern Italy: Implications in Screening for the Disease and Phenotype Characterization for Patients with Homozygote Mutations

Giuseppe Castaldo1,2, Antonella Fuccio1, Cécile Cazeneuve3, Luigi Picci4, Donatello Salvatore5, Valeria Raia6, Maurizio Scarpa4, Michel Goossens3 and Francesco Salvatore1,a

1 Centro di Ingegneria Genetica scarl and Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli "Federico II", 80131 Naples, Italy.

2 Facoltà di Scienze, Università del Molise, I-86170 Isernia, Italy.

3 Laboratoire de Biochimie et de Génétique Moléculaire, INSERM U468, Hôpital Henri-Mondor, F-94010 Créteil, France.

4 Dipartimento di Pediatria, Università di Padova, I-35100 Padua, Italy.

5 Divisione di Pediatria, Ospedale Civile, I-85100 Potenza, Italy.

6 Dipartimento di Pediatria, Università di Napoli "Federico II", 80131 Naples, Italy.
a Address correspondence to this author at: Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli "Federico II", via S. Pansini 5, 80131 Napoli, Italy. Fax 39 081 746 3650; e-mail salvator{at}unina.it

Background: The search for the eight most frequent mutations (i.e., {Delta}F508, G542X, W1282X, N1303K, 1717-1G->A, R553X, 2183AA->G, and I148T) by allele-specific oligonucleotide dot-blot analysis revealed 78% of 396 cystic fibrosis alleles in Southern Italy. The observation of frequent haplotypes on the unidentified cystic fibrosis alleles suggested that a few mutations could account for a large number of unidentified alleles.

Methods: We screened most of the coding sequence of the cystic fibrosis transmembrane regulator gene by denaturing gradient gel electrophoresis to determine the spectrum of these mutations in 68 unrelated cystic fibrosis patients bearing one or both unidentified mutations.

Results: The screening revealed five mutations, R1158X, 711+1G->T, 4016insT, L1065P, and G1244E, each of which had a frequency of 1.3–1.8% (7% collectively). The 7% increase in the detection rate (85% vs 78%) reduces by >50% the residual risk of being cystic fibrosis carriers for couples who had tested negative by molecular analysis. We therefore designed a second allele-specific oligonucleotide set to analyze the five mutations. Among the patients analyzed, one patient homozygous for the L1065P mutation expressed a mild pulmonary and intestinal form of the disease with pancreatic insufficiency. Two other patients, homozygous for mutations R1158X and 4016insT, both expressed a severe cystic fibrosis phenotype.

Conclusions: Five cystic fibrosis mutations are peculiar to patients from Southern Italy. The method described for their analysis is efficient, inexpensive, and can be semi-automated by use of a robotic workstation. The results obtained in patients from Southern Italy may have an impact on laboratories in other countries, given the large migrations of populations from Southern Italy to other countries in the last two centuries.© 1999 American Association for Clinical Chemistry




The following articles in journals at HighWire Press have cited this article:


Home page
 Clin. Chem.Home page
A. Elce, A. Boccia, G. Cardillo, S. Giordano, R. Tomaiuolo, G. Paolella, and G. Castaldo
Three Novel CFTR Polymorphic Repeats Improve Segregation Analysis for Cystic Fibrosis
Clin. Chem., July 1, 2009; 55(7): 1372 - 1379.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
K. J. Friedman and L. M. Silverman
Cystic Fibrosis Syndrome: A New Paradigm for Inherited Disorders and Implications for Molecular Diagnostics
Clin. Chem., July 1, 1999; 45(7): 929 - 931.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Association for Clinical Chemistry.