L206W mutation of the cystic fibrosis gene, relatively frequent in French Canadians, is associated with atypical presentations of cystic fibrosis

Abstract

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 400 mutations have been reported at this locus. Although severe forms of cystic fibrosis are usually associated with pancreatic insufficiency, pulmonary dysfunction, and elevated sweat chloride, there is a wide range of phenotypes, including congenital absence of the vas deferens, observed with some of the milder mutations. The L206W mutation, which was first identified in patients from South France, is relatively frequent in French Canadians from Quebec. In this report, we document the atypical form of cystic fibrosis associated with this mutation, in a cohort of 7 French Canadian probands.

A randomized, double-blind study comparing the effects of beclomethasone and fluticasone on bone density over two years

“…However, the absence of significant change in the PD with isoprenaline stimulation was highly suggestive for CF, a diagnosis confirmed by genotype analysis which revealed DF508/ L206W mutations. The L206W mutation, located in exon 6a, is usually associated with a mild CF phenotype (bronchiectasis or CBAVD alone) or even asymptomatic presentations of CF [12,13].…”

“…Principal aetiological factors for diffuse bronchiectasis include infectious injuries during childhood, primary ciliary dyskinesia, and mucus disorders. However, the nosological limit between CF and disseminated bronchiectasis remains vague as: 1) classical CF has long been recognized as a cause of disseminated bronchiectasis [7]; 2) an increased incidence of heterozygous DF508 mutations in the CF gene has been repetitively reported in patients with bronchiectasis [8± 11]; and 3) disseminated bronchiectasis may represent the unique clinical symptom in mild forms of genetically proven CF in adult patients [12,13]. Similarly, the limits between isolated CBAVD and CF are also subject to discussion as: 1) patients with CBAVD have an abnormally high incidence of heterozygous mutations in the CF gene [14]; and 2) CBAVD may represent the unique clinical manifestation of a mild CF disease [15].…”

CFTR mutation distribution among U.S. Hispanic and African American individuals: Evaluation in cystic fibrosis patient and carrier screening populations

“…In the carrier screening group, 4 mutations, D1152H, R117H, ⌬I507, and L206W, had frequencies of 3.8% to 6.2%, whereas the same mutations were either observed only once or not at all in the CF patient population. With the exception of ⌬I507, each of these mutations is associated with variable phenotypic expression [21][22][23][24][25][26] and when paired with ⌬F508 has been reported in individuals with cystic fibrosis as well as CAVD. 24 African American CF patient population Table 2 depicts the distribution of 33 CFTR mutations identified in the African American population.…”

Misprocessing of theCFTRprotein leads to mild cystic fibrosis phenotype

“…Individuals bearing p.L206W in trans with the severe CF-causing mutation p.F508del (DF508) may have CF or isolated CBAVD [Claustres et al, 2000;Desgeorges et al, 1995;Rozen et al, 1995]. Its relative frequency is estimated to range 0.2 to 0.4% of 7,420 CF chromosomes in France [Claustres et al, 2000] and raised 0.8% of CF chromosomes in a study in Brazil [Bobadilla et al, 2002;Claustres et al, 2000].…”