Male infertility as the only presenting sign of cystic fibrosis when homozygous for the mild mutation R117H.

Male infertility as the only presenting sign of cystic fibrosis when homozygous for the mild mutation R117H Since the identification of the cystic fibrosis gene (CFTR),' more than 265 mutations have been described (CF Genetic Analysis Consortium, 1992). The most common disease causing mutation, AF508, occurs in approximately 70% of CF chromosomes and causes moderate to severe disease,' with variable prevalence in populations of different ethnic origins. Among the numerous rare mutations, Rl 17H (a G to A transition at nucleotide 482) produces a missense amino acid substitution (arginine to histidine) in the first transmembrane domain of CFTR. It has only been reported in the heterozygous state, usually with AF508 occurring in the other CFTR gene; the compound heterozygotes are mildly affected.'6 We have studied a 30 year old French male with sterility owing to congenital bilateral absence of the vas deferens (CBAVD). He is homozygous for the R117H CFTR mutation , which was detected by DGGE screening and characterised by direct sequencing of PCR amplified DNA from exon 4 using the Sequenase USB kit. The subject has no respiratory or pancreatic involvement and has a normal sweat electrolyte value. His parents are not consanguineous and there are no other cases of CBAVD or CF in his family. Based on the primary finding of a higher rate of AF508 heterozygosity in infertile males,78 it has recently been suggested that isolated CBAVD might represent a primary genital form of CF.9'0 Several males presenting with infertility have been found to be heterozygotes for AF508 and other known mutations and on investigation have mild CF with normal or raised sweat electrolytes and subclinical lung disease. However, this is the first report of homozygosity for Rl 17H. It results in a clinical presentation of CBAVD cystic fibrosis completely devoid of the classical symptoms of CF. Among the reported cases of rare alleles of CFTR found in compound heterozygotes, the RI 17H mutation seems to be highly represented. It should be systematically screened for in all patients with CBAVD, as it may represent a common CF mutation causing very mild disease, with infertility as the only clinical presentation. Identification of the cystic fibrosis gene: chromosome walking and jumping. mutations in highly conserved residues are found in mildly affected cystic fibrosis patients. 4 Mickle JE, Oates RD, Anguiano A, et al. A frequent compound heterozygous cystic fibro-sis genotype in males with congenital bilateral absence of the …