<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the <italic>CFTR</italic> gene. The knowledge of <italic>CFTR</italic> mutations present in certain population is important for designing a simple, fast and cost-effective genetic testing approach, also for better management of CF patients, including the administration of novel targeted therapies. Here, we present genetic results of 158 unrelated CF patients from the National CF Registry of the Republic of North Macedonia. Initially, patients were screened for the 11 most common CF mutations. Additional CF mutations and large deletions/duplications in the <italic>CFTR</italic> gene were analyzed using commercial kits. If the genotype was undetermined, all <italic>CFTR</italic> exons were analyzed using Sanger DNA sequencing or next generation sequencing (NGS) (since 2014). The most common CF mutation, c.l521_ 1523del (legacy name F508del), was found with an overall incidence of 75.9%. Additionally, 26 other pathogenic variants and three large deletions were identified in the <italic>CFTR</italic> gene as a genetic cause of CF. Two of these, c.1070 C>T (p.Ala357Val) and c.2779_2788dup CTTGCTATGG (p.Gly930AlafsTer48), were novel. According to the distribution and prevalence of the pathogenic variants detected in our patients, a fast and cost-effective method, based on a single base extension was designed as a first-line CF genetic test with a 90.0% detection rate within our population. Furthermore, the knowledge of <italic>CFTR</italic> mutation classes in our CF patients represents the first step toward personalized therapy for CF in our country.</p></abstract>

The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the CFTR gene. The knowledge of CFTR mutations present in certain population is important for designing a simple, fast and cost-effective genetic testing approach, also for better management of CF patients, including the administration of novel targeted therapies. Here, we present genetic results of 158 unrelated CF patients from the National CF Registry of the Republic of North Macedonia. Initially, patients were screened for the 11 most common CF mutations. Additional CF mutations and large deletions/duplications in the CFTR gene were analyzed using commercial kits. If the genotype was undetermined, all CFTR exons were analyzed using Sanger DNA sequencing or next generation sequencing (NGS) (since 2014). The most common CF mutation, c.l521_ 1523del (legacy name F508del), was found with an overall incidence of 75.9%. Additionally, 26 other pathogenic variants and three large deletions were identified in the CFTR gene as a genetic cause of CF. Two of these, c.1070 C>T (p.Ala357Val) and c.2779_2788dup CTTGCTATGG (p.Gly930AlafsTer48), were novel. According to the distribution and prevalence of the pathogenic variants detected in our patients, a fast and cost-effective method, based on a single base extension was designed as a first-line CF genetic test with a 90.0% detection rate within our population. Furthermore, the knowledge of CFTR mutation classes in our CF patients represents the first step toward personalized therapy for CF in our country.

Cystic fibrosis mutation spectrum in north macedonia: A step toward personalized therapy

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the CFTR gene. The...

Cystic fibrosis mutation spectrum in north macedonia: A step toward personalized therapy

Article Category: Original Article

Publicado en línea: 28 ago 2019

Páginas: 35 - 40

DOI: https://doi.org/10.2478/bjmg-2019-0009

Palabras clave
Cystic fibrosis (CF), mutation classes, Mutations

© 2019 Terzic M, Jakimovska M, Fustik S, Jakovska T, Sukarova-Stefanovska E, Plaseska-Karanfilska D, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Cystic fibrosis mutation spectrum in north macedonia: A step toward personalized therapy

Article Category: Original Article

Publicado en línea: 28 ago 2019

Páginas: 35 - 40

DOI: https://doi.org/10.2478/bjmg-2019-0009

Palabras claveCystic fibrosis (CF), mutation classes, Mutations

© 2019 Terzic M, Jakimovska M, Fustik S, Jakovska T, Sukarova-Stefanovska E, Plaseska-Karanfilska D, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Palabras clave
Cystic fibrosis (CF), mutation classes, Mutations