Background: In this study the authors present an update to the CFTR mutation profile in Hungary, utilizing data from a selected cohort of 45 cystic fibrosis (CF) patients from different regions of the country.
Methods: Depending on the preceding analysis, four different mutation detection methods were used. A commercial assay targeting the most common CF-causing mutations was performed as the first test followed by an allele specific PCR for CFTRdele2,3(21kb), Sanger sequencing and MLPA analysis of the coding region of the CFTR gene.
Results: In our recent study 27 different mutations were detected, including 2 novel ones (c.1037_1038insA and c.1394C>T). Besides F508del (c.1521_1523delCTT), the following mutations were found at a frequency of ≥ 4.0%: W1282X (c.3846G>A), N1303K (c.3909C>G), CFTRdele2,3(21kb) (c.54-5940_273+10250del21kb) and 2184insA (c.2052_2053insA). In addition, four mutations (G542X, Y1092X, 621+1G>T, and 2143delT) were found in more than one allele.
Conclusions: The updated database of Hungarian mutations not only enables to increase the efficiency of the existing diagnostic approach, but also provides a further refined basis for the introduction of the molecular newborn screening (NBS) program in Hungary.
Uvod: U ovoj studiji autori predstavljaju nove podatke dobijene izučavanjem profila mutacije CFTR u Mađarskoj uz pomoć podataka izabrane grupe od 45 pacijenata sa cističnom fibrozom (CF) iz različitih krajeva zemlje.
Metode: U zavisnosti od prethodne analize, korišćene su četiri različite metode za detekciju mutacija. Prvo je rađen komercijalni test koji ciljano traga za najčešćim mutacijama koje izazivaju CF, posle čega su primenjeni PCR za CFTRdele2,3(21 kb), Sanger sekvenciranje i MLPA analiza kodirajućeg regiona gena CFTR.
Rezultati: U našoj nedavnoj studiji otkriveno je 27 različitih mutacija, uključujući dve dotad nepoznate (c.1037_1038insA i c.1394C>T). Pored F508del (c.1521 _1523delCTT), pronađene su sledeće mutacije sa učestalošću ≥ 4,0%: W1282X (c.3846G>A), N1303K (c.3909C >G), CFTRdele2,3(21kb) (c.54-5940_273+10250 del21kb) i 2184insA (c.2052_2053insA). Pored toga, četiri mutacije (G542X, Y1092X, 621+1G>T i 2143 delT) nađene su u više od jednog alela.
Zaključak: Baza podataka o mađarskim mutacijama dopunjena poslednjim informacijama ne samo da omogućava povećavanje efikasnosti postojećeg dijagnostičkog pristupa, već takođe pruža dodatno usavršen osnov za uvođenje programa molekularnog skrininga novorođenčadi (NBS) u Mađarskoj.
Keywords: cystic fibrosis; mutational spectrum; newborn screening.