Clinical and Genetic Characterisation of Cystic Fibrosis Patients in Latvia: A Twenty-Five-Year Experience

Abstract

Cystic fibrosis (CF) is the most common life-limiting genetic disorder in European descent populations. It is caused by pathogenic variants in the CFTR gene, and inheritance is autosomal recessive. This study provides an up-to-date, comprehensive estimation of the distribution of CFTR pathogenic variants in Latvia and their phenotypic characteristics. It also reports the first results of the CF newborn screening programme following its implementation in 2019. We analysed the clinical and molecular data of CF patients treated at the only tertiary hospital in Latvia providing specialised healthcare for the disorder. Between 1997 and 2022, 66 CF patients from 62 families were diagnosed based on symptoms or a molecular confirmation (six patients were diagnosed through the CF newborn screening programme). F508del was identified in 70.5% of all CF chromosomes. Known variants were identified in more than one family: dele2,3, R1006H, L1335P, W57R, R553X, 2143delT and 3849+10kb C>T (legacy names used). Furthermore, two novel variants were identified, namely, c.503C>A p.(Ser168Ter) and c.(743+1_744-1)_(1584+1_1585-1)del p.(?). The available follow-up results indicated that Latvian CF patients demonstrated similar tendencies to CF patients worldwide. The oldest age at diagnosis prior to the implementation of the CF newborn screening programme was 14 years. We provide here, for the first time, a comprehensive description of Latvian CF patients. An improvement in the healthcare of CF patients over time, including access to diagnosis, is evident. Two novel CF-causing variants are reported, and F508del is the most frequently occurring variant in the population, thus suggesting that F508del screening should be followed by the testing of the full CFTR gene.

Keywords

• cystic fibrosis
• CFTR
• novel variants