Spectrum of CFTR Mutations on Reunion Island: Impact on Neonatal Screening

The large heterogeneity in the cystic fibrosis (CF) gene is the main difficulty for genotype characterization. Numerous studies have re- ported considerable variations in frequencies of CF transmembrane conduc- tance regulator (CFTR) mutations in different populations, such as African, Asian, or European populations. To completely characterize the spectrum of mutations in the CFTR gene in the Reunion Island population, we screened 228 CF chromosomes using denaturing high-pressure liquid chromatography and denaturing gradient gel electrophoresis following by direct sequencing. We identified 27 mutations, accounting for 93% of CF chromosomes. They included three novel mutations (M1T, 3121-3CVG, and L1324P), which are described in this paper. The detection of such a high proportion of Reunion Island CFTR mutations is important for improving neonatal screening of CF on Reunion Island. Reunion Island, which is situated not far from the Tropic of Capricorn in the southwestern Indian Ocean, is a French province, 800 km east of Madagascar and 200 km west of Mauritius. For three and a half centuries, inhabitants settled on this desolate island, coming from France, other areas of Europe, different regions of Africa (Madagascar, East Africa, Comores), and Asia (South India, Gujarat, China). On Reunion Island the birth prevalence of cystic fibrosis (CF) is particularly high in the population of European origin, approximately 1:1000 (F. Pierson, personal communication, 1990). In a previous paper we demonstrated that the screening of the 27 exons of the CF transmembrane conductance regula- tor (CFTR) gene in 69 CF families allowed the detection of 91% of the molecular defects present on Reunion Island (Cartault et al. 1998). In this paper we present an update on the spectrum of CFTR mutations on Reunion Island from a study of 114 CF families. We have identified 27 different mutations (including 3 novel