DOES MALE FERTILITY IMPAIRMENT DUE TO IDIOPATHIC SEMEN HYPERVISCOSITY DEPEND ON CFTR GENE MUTATIONS?

Some DNA sequence variations of CFTR gene — the mutations of which cause Cystic Fibrosis (CF) — arise in exons (i.e. segments of the gene that, after transcription into messenger RNA, are translated into the aminoacidic sequence of protein); some others arise in introns (i.e. segments of the gene that are excised from RNA sequence before its translation into the aminoacidic sequence of protein). CF caused by this latter kind of sequence variations are often atypical forms of CF (generally non severe, in some cases monosymptomatic) characterised by highly variable clinical manifestations. Due to this high variability, these forms may be difficult to diagnose, with consequent therapeutic treatment delay and loss of genetic test sensitivity. A well known CF form of this kind is male infertility due to congenital bilateral absence of vas deferens. Our research group proposed, following results of a preliminary genetic analysis, that also male impaired fertility due to seminal fluid hyperviscosity (not responding to conventional therapy) is a mild form of CF. The aim of this project is to definitively establish the link between male impaired fertility due to seminal fluid hyperviscosity and CFTR mutations. This aim will be reached by an extended genetic and functional analysis (at messenger RNA level) of CFTR in selected subjects affected by this disease. These studies may help: 1) to extend the known spectrum of disease causing mutations of CFTR, improving diagnostic panels; 2) to possibly characterize men with impaired fertility based on seminal fluid hyperviscosity as subjects at risk of CF and address them to appropriate diagnostic, therapeutic and follow-up procedures; 3) to contribute to the clarification of the correlation between DNA sequence variations of CFTR (genotype) and clinical manifestations (phenotype).