Complete screening of the CFTR gene in Argentine cystic fibrosis patients

Abstract

In order to establish the nature and the distribution of mutations causing cystic fibrosis (CF) in 220 unrelated Argentine families, the present authors conducted an extensive molecular analysis of the CF transmembrane regulator (CFTR) gene. First, a direct mutation analysis of 13 common mutations was done, enabling the detection of 319 out of 440 CF alleles (72.52%). Then an exhaustive screening of the entire coding region and the adjacent sequences of the CFTR gene was performed in all patients carrying at least one unidentified CF allele using the multiplex heteroduplex analysis assay followed by direct DNA sequencing. Thirty-nine different CF mutations, including five previously undescribed mutations (i.e. L6V, Y362X, 1353insT, 2594delGT and 2686insT) and two novel polymorphisms (i.e. 1170G/C and 3315A/C) were identified. As a result, the overall detection rate increased by up to 83.45%. Besides DeltaF508, only five mutations showed frequencies higher than 1%. In addition, a total of 49% of the mutations were rare because they were found in only one CF family. This wide spectrum of CF mutations is in agreement with the heterogeneous ethnic origin of the Argentine population. The data obtained here may have important consequences for the development of adequate strategies for the molecular diagnosis of CF in Argentina.

Carrier frequency of the 35delG and A1555G deafness mutations in the Argentinean population

“…In the present study, the frequency found was 1/65, which is in agreement with the expected value. This carrier frequency was similar to that estimated for the most common cystic fibrosis mutation, DF508, in the Argentinean population [26,27].…”

CFTR gene analysis in Latin American CF patients: Heterogeneous origin and distribution of mutations across the continent

“…In the last decade, some countries began screening for particular mutations, and only recently four Latin American countries, namely Argentina [11,12], Mexico [13], Colombia [14] and Brazil [15], reported extensive CFTR locus (MIM # 602421) analyses. Still, few data are available for some of the rest of the Latin American and Caribbean countries and for others there are no data at all.…”

Genetic testing and services in Argentina

“…Newborn screening detects three autosomal recessive conditions. Their birth prevalences are: PKU 1/30,000, cystic fibrosis 1/9,000, and congenital adrenal hyperplasia 1/15,000 (Chertkoff et al 1997;Visich et al 2002;Pesquisa Neonatal 2007). Geographical clusters of single-gene disorders, usually due to founder effects, have been described but are rare (Castilla and Sod 1990).…”