ABCMdb

PMID: 15666307

Salvatore D, Tomaiuolo R, Vanacore B, Elce A, Castaldo G, Salvatore F
Isolated elevated sweat chloride concentrations in the presence of the rare mutation S1455X: an extremely mild form of CFTR dysfunction.
Am J Med Genet A. 2005 Mar 1;133A(2):207-8., 2005-03-01 [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Ser1455* American Journal of Medical Genetics 133A:-208 (2005) Clinical Report Isolated Elevated Sweat Chloride Concentrations in the Presence of the Rare Mutation S1455X: An Extremely Mild Form of CFTR Dysfunction Donatello Salvatore,1 * Rossella Tomaiuolo,2 Borghina Vanacore,2 Ausilia Elce,2 Giuseppe Castaldo,2,3 and Francesco Salvatore2 1 Pediatric Division, Cystic Fibrosis Center, San Carlo Hospital, Potenza, Italy 2 CEINGE-Advanced Biotechnologies and Department of Biochemistry and Medical Biotechnologies, University of Naples ''Federico II``, Naples, Italy 3 Faculty of Sciences, University of Molise, Isernia, Italy Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been shown to cause typical cystic fibrosis (CF) and several milder phenotypes. Login to comment 1 ABCC7 p.Ser1455* We report on two asymptomatic sisters who had isolated increased sweat chloride concentrations, and in whom systematic scanning of the whole coding region of the CFTR generevealedtheF508del/S1455X genotype. Login to comment 9 ABCC7 p.Ser1455* Mickle et al. [1998] described a mother and a daughter who had isolated elevated sweat chloride concentrations, and the non-sense mutation S1455X in compound heterozygosis with the del14a deletion [Mickle et al., 1998]. Login to comment 10 ABCC7 p.Ser1455* We report on two asymptomatic sisters who had increased sweat chloride concentrations, and in whom systematic scanning of the whole coding region of the CFTR gene revealed the F508del/S1455X genotype. Login to comment 27 ABCC7 p.Ser1455* The analysis revealed the non-sense mutation S1455X, in compound heterozygosity with F508del. Login to comment 35 ABCC7 p.Ser1455* E-mail: saverdon@tiscali.it Received 31 March 2004; Accepted 21 October 2004 DOI 10.1002/ajmg.a.30518 ß 2005 Wiley-Liss, Inc. and gene scanning confirmed the presence of the F508del/ S1455X genotype (Table I). Login to comment 37 ABCC7 p.Ser1455* The analysis revealed the presence of the mutation F508del in heterozygosis in the mother and of the mutation S1455X in heterozygosis in the father. Login to comment 38 ABCC7 p.Ser1455* DISCUSSION Our case report confirms that S1455X is a rare mutation associated with isolated elevated sweat chloride concentrations in the absence of the CF phenotype. Login to comment 39 ABCC7 p.Ser1455* Although, we cannot exclude changes in the patients` clinical conditions in the future, the long follow-up (8 years) of these two sisters and the normal clinical picture of the previously reported patients, indicate that S1455X is related to the isolated sweat gland dysfunction [Moyer et al., 1999]. Login to comment 40 ABCC7 p.Ser1455* The possible explanation of this phenotype is that the CFTR mRNA transcript bearing the S1455X mutation is stable, and encodes a version of CFTR that lacks the last 26 amino acids, which is processed to a mature state and functions similarly to wild-type CFTR [Mickle et al., 1998]. Login to comment 41 ABCC7 p.Ser1455* In addition, the S1455X CFTR mutation is mispolarized to the lateral membrane of epithelial cells [Moyer et al., 1999]. Login to comment 42 ABCC7 p.Ser1455* The transport of the electrolytes across the respiratory epithelia should be studied in vivo by means of measurement of nasal potential difference (NPD) in patients carrying the S1455X mutation, in order to evaluate the organ specific expression of the mutated gene, the hypothesis being that sodium and chloride transport might be normal or near normal at the level of airway epithelial cells despite the abnormal sweat electrolytes. Login to comment 45 ABCC7 p.Ser1455* The most distal CF-associated mutation reported is a missense mutation predicted to replace aspartic acid for asparagine at amino acid 1445 [Cystic Fibrosis Genetic Analysis Consortium, 2004], whereas mutations more distal with respect to S1455X have been associated to the congenital bilateral absence of vasa deferentes. Login to comment 46 ABCC7 p.Ser1455* All compound heterozygotes with the S1455X mutation so far reported are female, so we cannot exclude the possibility that this mutation in males would be related to isolated elevated sweat chloride and infertility. Login to comment 47 ABCC7 p.Ser1455* The fact that a very mild phenotype is associated with S1455X is important for genetic counseling. Login to comment 49 ABCC7 p.Ser1455* In the case of our adult patient, we calculated the risk of having a CF child of 1:334, but the risk could be further ''halved`` based on the hypothesis that a S1455X compound heterozygote would be asymptomatic. Login to comment