Cluster of cystic fibrosis cases in a limited area of Brittany (France)

Cystic fibrosis in the northern sector of the French "département" of Finistère is 1:1787 live births. Within this sector a concentration of the disease was found in a small area. The minimal frequency in this area, from 1946 to 1972, was calculated as 1 per 377 live births, the gene frequency being 0.0515. Genealogic analysis, going back to the beginning of the 18th century, showed a relationship between 8 of the 10 families to which the patients belonged. The origin of the deleterious genes may be explained by at least five primary ancestral couples living in the 18th century. Random drift is the most probable explanation for the concentration of cystic fibrosis in this region.     

CFTR mutation analysis and haplotype associations in CF patients

Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and portions of all introns were sequenced and large insertions/deletions were characterized as well as two intronic di-nucleotide microsatellites. For CF patient samples, at least two mutations were identified/verified and four specimens contained three likely CF-associated mutations. Thirty-four sequence variations in 152 chromosomes were identified, five of which were not previously reported. Twenty-seven of these variants were used to predict haplotypes from the major haplotype block defined by HapMap data that spans the promoter through intron 19. Chromosomes containing the F508del (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a common haplotype subgroup, consistent with a common ancient European founder. Understanding the haplotype background of CF-associated mutations in the U.S. population provides a framework for future phenotype/genotype studies and will assist in determining a likely cis/trans phase of the mutations without need for parent studies.     

Reproductive attitudes of couples having a child with cystic fibrosis in Brittany (France)

Cystic fibrosis (CF) has an incidence of one in 2,636 livebirths and a carrier rate of one in 26 inhabitants in Brittany. One objective of a major enquiry among parents having a CF child as well as CF adolescents and adults was to evaluate the reproductive behavior of 124 couples attending a CF care center. Knowledge of recurrence risk resulted in deciding against further progeny or in reducing the number of children (average number of children: 1.96; ideal mean number of children: 3.7). Thirty-five percent adopted or changed their method of contraception after the birth of their affected child, but the change was due to the birth of the CF child in only 14.3% of the couples. Prenatal diagnosis (PD) was favored by 95.1%, and 41.2% had used it; 68.6% were in favor of pregnancy interruption for CF and 76.2% would interrupt the pregnancy should PD reveal that their fetus had CF. All 123 respondents thought that genetic counseling was useful, but only 87.1% knew of its availability. Our results are quite different from those previously published. Although results could be population-specific, one cannot exclude the fact that they reflect a change of attitudes among parents, the other studies being much older.     

先天性单侧输精管缺如患者CFTR基因突变研究

目的 探讨囊性纤维跨膜转运调节物（ｃｙｓｔｉｃ ｆｉｂｒｏｓｉｓ ｔｒａｎｓｍｅｍｂｒａｎｅ ｃｏｎｄｕｃｔａｎｃｅ ｒｅｇｕｌａｔｏｒ,ＣＦＴＲ）基因在中国人先天性单侧输精管缺如（ｃｏｎｇｅｎｉｔａｌ ｕｎｉｌａｔｅｒａｌ ａｓｅｎｃｅｏｆ ｔｈｅ ｖａｓ ｄｅｆｅｒｅｎｓ,ＣＵＡＶＤ）患者中的突变频率及热点。方法 应用聚合酶反应－单链构象多态（ＰＣＲ－ＳＳＣＰ）、３银染技术及ＰＣＲ产物直接序     

Comparison of genetic profiles of Campylobacter strains isolated from poultry, pig and Campylobacter human infections in Brittany, France

Five hundred eighty-two Campylobacter isolates (177 from humans, 319 from poultry and 86 from pig) collected in Brittany, France, in 2003 and 2004 were typed by pulsed-field gel electrophoresis. The number of human cases increased during the hot season, particularly for C. jejuni. Twelve genetic groups out of 27 contained human isolates collected over the two years. These groups had 21.3 and 17.0% of the isolates obtained in 2003 and 2004, respectively. In four cases, isolates from 2003 have the same Pulsed-field gel electrophoresis (PFGE) profile as isolates from 2004. Six PFGE profiles common to poultry and human isolates were identified. Poultry isolates were found in 47 clusters containing human isolates. Caeca from farms and slaughterhouses accounted for 66% of these isolates, with chicken legs obtained from supermarkets accounting for the other 34%. Pig isolates never clustered with poultry and human isolates. In conclusion, the analysis of the genetic profiles of Campylobacter resulting from human cases showed that there were few identical or genetically close isolates between the human cases declared in 2003 and those declared in 2004. This highlighted a great genetic diversity in the isolates and indicated that it should be difficult to bind the human infections with groups of Campylobacter isolates presenting particular genetic profiles. The Campylobacter isolates obtained from the two animal production systems had different genotypes, and isolates from pigs differed genetically from isolates obtained from humans. We found that 44.6% of human Campylobacter isolates were genetically related to genotypes found in poultry and a part of these campylobacteriosis are due to contact with poultry. This is not particularly surprising in Brittany, a farming area with many animal-rearing farms and slaughterhouses. This work highlights the implication of the poultry in the French human cases and that handling of poultry is also an important risk for Campylobacter infection in humans.     

Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling

BACKGROUND: Mutations in the cystic fibrosis (CF) transmembrane conductanceregulator (CFTR) gene have been widely detected in infertilemen with congenital bilateral absence of the vas deferens (CBAVD).Despite extensive analysis of the CFTR gene using varied screeningmethods, a number of cases remain unsolved and could be attributableto the presence of large gene rearrangements, as recently shownfor CF patients. METHODS: We carried out a complete CFTR gene study in a group of 222CBAVD patients with strict diagnosis criteria and without renalanomaly, and searched for rearrangements using a semi-quantitativeassay in a subgroup of 61 patients. RESULTS: The overall mutation detection rate was 87.8%, and 82% of patientscarried two mutations. Ten out of the 99 different mutationsaccounted for 74.6% of identified alleles. Four large rearrangementswere found in patients who already carried a mild mutation:two known partial deletions (exons 17a to 18 and 22 to 23),a complete deletion and a new partial duplication (exons 11to 13). The rearrangements accounted for 7% of the previouslyunknown alleles and 1% of all identified alleles. CONCLUSIONS: Screening for rearrangements should be part of comprehensiveCFTR gene studies in CBAVD patients and may have impacts ongenetic counselling for the patients and their families.