Dirami et al. (2013) studied 3 men with primary infertility and moderate to severe asthenozoospermia associated with mutations in the SLC26A8 gene (see MOLECULAR GENETICS). The first was a 44-year-old man who had low ejaculate volume and a ... Dirami et al. (2013) studied 3 men with primary infertility and moderate to severe asthenozoospermia associated with mutations in the SLC26A8 gene (see MOLECULAR GENETICS). The first was a 44-year-old man who had low ejaculate volume and a frequency of sperm morphologic abnormalities moderately higher than normal, with 19% coiled tails and 63% abnormally shaped posterior sperm heads; he also had increased polymorphonuclear leukocytes. He was an only child with an unknown father; his mother had 1 brother with no children. The second was a 42-year-old man with flagellar defects in about 10% of sperm, although other semen parameters were normal. He had 2 sisters and 4 brothers, all of whom had children. The third was a 31-year-old man who had a low sperm count and a very high frequency of combined morphologic defects, including abnormal head shape (98%), midpiece abnormalities (27%), and flagellar defects (38%). He was conceived after primary infertility of 10 years' duration, and was an only child like his father; his mother had 1 brother and 1 sister with children. In all 3 patients, no bacteria were detected in semen cultures.
In a cohort of 146 men being treated for infertility, Dirami et al. (2013) analyzed the coding sequence of the candidate gene SLC26A8 by DHPLC and direct sequencing and identified heterozygosity for 3 missense mutations in 3 men ... In a cohort of 146 men being treated for infertility, Dirami et al. (2013) analyzed the coding sequence of the candidate gene SLC26A8 by DHPLC and direct sequencing and identified heterozygosity for 3 missense mutations in 3 men (608480.0001-608481.0003, respectively). No family members were available for genetic study. The mutations were not present in 121 ethnically matched controls, and for all 3 variants, the frequency of the mutant allele was significantly higher in the cohort of asthenozoospermic individuals than in 8,600 controls of unknown sex and fertility status. Analysis of physical interactions between the mutant SLC26A8 and CFTR (602421), a protein present in mature sperm and required for sperm motility and capacitation, showed that although protein-protein interactions were partly conserved, the capacity to activate CFTR-dependent anion transport was completely abolished for all 3 mutants.