Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues.
OBJECTIVE
Screening for mutations in the entire Cystic Fibrosis gene (CFTR) of Brazilian infertile men with congenital absence of vas deferens, in order to prevent transmission of CFTR mutations to offspring with the use of assisted reproductive technologies.


METHODS
Specific polymerase chain reaction (PCR) primers were designed to each of the 27 exons and splicing sites of interest followed by single strand conformational polymorphism and Heteroduplex Analysis (SSCP-HA) in precast 12.5% polyacrylamide gels at 7 masculineC and 20 masculineC. Fragments with abnormal SSCP migration pattern were sequenced.


RESULTS
Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in hetrozygosis.


CONCLUSIONS
The available screenings for CF mutations do not include the atypical mutations associated to absence of vas deferens and thus, when these tests fail to find mutations, there is still a genetic risk of affected children with the help of assisted reproduction. We recommend the screening of the whole CFTR gene for these infertile couples, as part of the work-up before assisted reproduction.
Pieri
Patricia de Campos
Pde C
Department of Pediatrics, São Paulo University, Medical College, São Paulo, Brazil. patricp@icr.hcnet.usp.br
Missaglia
Mariangela Tuzzollo
MT
Roque
Juliana de Almeida
Jde A
Moreira-Filho
Carlos Alberto
CA
Hallak
Jorge
J
D000328:Adult; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005817:Genetic Counseling; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014649:Vas Deferens / Q000002:abnormalities*