In 1988, an excess of male carriers of cystic fibrosis (CF) mutations among sibs of CF patients was reported by Kitzis et al. [1]. In particular, a significant deviation from a 1:1 sex ratio was observed among heterozygous carriers in favor of males, and among homozygous normals in favor of females. When the study reported by Kitzis et al. [1] was carried out, before the identification of the CFTR gene, carriers were detected by means of RFLPs tightly linked to the CF locus. Following the identification of the CFTR gene, direct carrier detection has become possible in those CF families where mutations are identified, thus avoiding possible errors deriving from misdiagnosis and/or recombination with the linked markers. We decided, therefore, to further investigate the question of a possible sex ratio distortion among carrier sibs of CF patients taking advantage of the large amount of data already available. Only families which were not included in the analysis done by Kitzis et al. [1], and in which both the paternal and the maternal mutations were identified, were included in the present analysis.

The sample of families was further subdivided into two groups: one composed of all families in which both parents were carriers of the ΔF508 mutation [2], and one in which only one parent was a ΔF508 carrier, while the other was a carrier of another known mutation. This subdivision allowed us to investigate the parental origin of the mutation in the second group of families. Results for the first group (both parents ΔF508 carriers) are shown in table 1. There is no deviation from the expected 2:1 ratio of heterozygotes to homozygotes among either the brothers or the sisters of CF patients in this group.

Table 1 Segregation of alleles in families with both parents ΔF508 carriers
Full size table

Results for the second sample are reported in table 2. There were 218 families in which the father was a ΔF508 carrier, and 198 in which the mother was a ΔF508 carrier. Although this is not a significant deviation from a 1:1 ratio, the following analysis was carried out separately in these two groups. The sex ratio among sibs was very close to 1:1 in both groups. Overall, boys were more likely to be carriers of ΔF508 or another mutation and girls were more likely to be noncarriers, independently of whether the ΔF508 mutation was coming from the father or the mother, but none of the observed proportions was significantly different from that expected under Mendelian segregation of the alleles.

Table 2 Segregation of alleles in families with only one parent a ΔF508 carrier
Full size table

In conclusion, there is no statistically significant indication in our sample of a segregation distortion; however, it is intriguing that, although not significant, the observed deviation is in the same direction of that observed by Kitzis etal. [1].