CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR). In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the fre...

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Autores principales:	Ewa Ziętkiewicz, Ewa Rutkiewicz, Andrzej Pogorzelski, Barbara Klimek, Katarzyna Voelkel, Michał Witt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be0cb2b8c56549daa7575f25ee624636
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spelling	oai:doaj.org-article:be0cb2b8c56549daa7575f25ee6246362021-11-18T08:30:58ZCFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.1932-620310.1371/journal.pone.0089094https://doaj.org/article/be0cb2b8c56549daa7575f25ee6246362014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586523/?tool=EBIhttps://doaj.org/toc/1932-6203Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR). In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the frequency profile characteristic for a given population. The goal of the study was to provide an updated comprehensive estimation of the distribution of CFTR mutations in Polish CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish population. The analyzed cohort consisted of 738 patients with the clinically confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one mutation in 14.8% of the affected individuals. The group composed of all the patients with only one or with no mutation detected (109 and 126 individuals, respectively) was analyzed further using a mutation screening approach, i.e. SSCP/HD (single strand conformational polymorphism/heteroduplex) analysis of PCR products followed by sequencing of the coding sequence. As a result, 53 more mutations were found in 97 patients. The overall efficiency of the CF allele detection was 82.5% (7.0% increase compared to INNOLiPA tests alone). The distribution of the most frequent mutations in Poland was assessed. Most of the mutations repetitively found in Polish patients had been previously described in other European populations. The most frequent mutated allele, F508del, represented 54.5% of Polish CF chromosomes. Another eight mutations had frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation distribution described herein is also relevant to the Polish diaspora. Our study also demonstrates that the reported efficiency of mutation detection strongly depends on the diagnostic experience of referring health centers.Ewa ZiętkiewiczEwa RutkiewiczAndrzej PogorzelskiBarbara KlimekKatarzyna VoelkelMichał WittPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89094 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ewa Ziętkiewicz Ewa Rutkiewicz Andrzej Pogorzelski Barbara Klimek Katarzyna Voelkel Michał Witt CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
description	Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR). In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the frequency profile characteristic for a given population. The goal of the study was to provide an updated comprehensive estimation of the distribution of CFTR mutations in Polish CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish population. The analyzed cohort consisted of 738 patients with the clinically confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one mutation in 14.8% of the affected individuals. The group composed of all the patients with only one or with no mutation detected (109 and 126 individuals, respectively) was analyzed further using a mutation screening approach, i.e. SSCP/HD (single strand conformational polymorphism/heteroduplex) analysis of PCR products followed by sequencing of the coding sequence. As a result, 53 more mutations were found in 97 patients. The overall efficiency of the CF allele detection was 82.5% (7.0% increase compared to INNOLiPA tests alone). The distribution of the most frequent mutations in Poland was assessed. Most of the mutations repetitively found in Polish patients had been previously described in other European populations. The most frequent mutated allele, F508del, represented 54.5% of Polish CF chromosomes. Another eight mutations had frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation distribution described herein is also relevant to the Polish diaspora. Our study also demonstrates that the reported efficiency of mutation detection strongly depends on the diagnostic experience of referring health centers.
format	article
author	Ewa Ziętkiewicz Ewa Rutkiewicz Andrzej Pogorzelski Barbara Klimek Katarzyna Voelkel Michał Witt
author_facet	Ewa Ziętkiewicz Ewa Rutkiewicz Andrzej Pogorzelski Barbara Klimek Katarzyna Voelkel Michał Witt
author_sort	Ewa Ziętkiewicz
title	CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
title_short	CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
title_full	CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
title_fullStr	CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
title_full_unstemmed	CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.
title_sort	cftr mutations spectrum and the efficiency of molecular diagnostics in polish cystic fibrosis patients.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/be0cb2b8c56549daa7575f25ee624636
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CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.

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