Distribution of CFTR mutations in Eastern Hungarians: Relevance to genetic testing and to the introduction of newborn screening for cystic fibrosis

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• 作者：Gergely Ivady^a ; Laszlo Madar^a ; Bela Nagy^b ; Ferenc Gonczi^c ; Eva Ajzner^d ; Erika Dzsudzsak^a ; Lenka Dvoř ; á ; ková ; ^e ; Eva Gombos^a ; Janos Kappelmayer^a ; Milan Macek Jr.^e ; Istvan Balogh^a ; ^{balogh@med.unideb.hu"" rel=""nofollow}
• 关键词：Cystic fibrosis ; Hungary ; Eastern Hungarians ; 2184insA ; CFTRdele2 ; 3(21 kb) ; DNA diagnostics ; Newborn screening
• 刊名：Journal of Cystic Fibrosis
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：10
• 期：3
• 页码：217-220
• 全文大小：208 K

文摘

Background

The aim of this study was characterization of an updated distribution of CFTR mutations in a representative cohort of 40 CF patients with the classical form of the disease drawn from Eastern Hungary. Due to the homogeneity of the Hungarian population our data are generally applicable to other regions of the country, including the sizeable diaspora.

Methods

We utilized the recommended “cascade” CFTR mutation screening approach, initially using a commercial assay, followed by examination of the common “Slavic” deletion CFTRdele2,3(21 kb). Subsequently, the entire CFTR coding region of the CFTR gene was sequenced in patients with yet unidentified mutations.

Results

The Elucigene CF29^Tm v2 assay detected 81.25 % of all CF causing mutations. An addition of the CFTRdele2,3(21 kb) increased the mutation detection rate to 86.25 % . DNA sequencing enabled us to identify mutations on 79/80 CF alleles. Mutations [CFTRdele2,3(21 kb), p.Gln685ThrfsX4 (2184insA) were found at an unusually high frequency, each comprising 5.00 % of all CF alleles.

Conclusion

We have identified common CF causing mutations in the Hungarian population with the most common mutations (p.Phe508del, p.Asn1303Lys, CFTRdele2,3(21 kb), 2184insA, p.Gly542X, and p.Leu101X), comprising over 93.75 % of all CF alleles. Obtained data are applicable to the improvement of DNA diagnostics in Hungary and beyond, and are the necessary prerequisite for the introduction of a nationwide “two tier” CF newborn screening program.