Spectrum of CFTR mutations in Argentine cystic fibrosis patients

Abstract

The identification of different mutations which cause cystic fibrosis (CF) in Argentine patients has been performed. Initially, 10 of the most commonly mutated loci in 228 independent chromosomes were analyzed. Each allele was detected by PCR amplification of DNA samples either directly on polyacrylamide gels, by restriction enzyme digestion and agarose gels electrophoresis, or by hybridization with allele specific oligonucleotides. The AF508 mutation was found in 57% of the alleles. The frequencies of the other CF mutations were as follows: G542X 3.9%, W1282X 3.1%, N1303K 1.7%, 1717 1‐G→A 0.9%, R553X 0.4%, R1162X 0.4%, whereas G551D, AI507 and S549N were not found. This direct mutation analysis enabled the detection of 155/228 CF alleles (67%). Of the remaining 73 unidentified CF alleles, 22 were investigated for the 27 exons by DGGE and 9 rare mutations were identified. The incidence of the main CF mutations analyzed was similar to that of the South European population and markedly different from other Latin American countries. The mutation data presented here may be useful for designing DNA testing strategies for CF in Argentina.

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

“…Some have concentrated in the search of specific mutations that are Mutation frequencies in Latin American CF patients most frequently found in Caucasians, by allele specific polymerase chain reaction (AS-PCR), enzymatic digestion, allele specific oligonucleotide hybridization (ASO), or using mainly commercial kits, whereas other studies used a systematic approach to analyse the promoter, coding and exon/ intron boundaries of the CFTR region in the search for any possible mutation. The methods used in the latter include Denaturing Gradient Gel Electrophoresis (DGGE), Single Strand Conformational Polymorphism (SSCP) and Heteroduplex Analysis methods, followed by sequencing of the observed electrophoretical variants [11][12][13][14][15].…”

“…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).…”

Argentina: Public Health Genomics

“…Research in clinical genetics is concentrated on dysmorphology/cytogenetics [30,31,32] and selected single gene disorders such as skeletal dysplasias [33], muscular dystrophies [34], fragile X syndrome [35], CF [36, 37], β-thalassemia [38], congenital deafness [39], and cancer [40,41,42,43]. …”