Globozoospermia is a rare phenotype of primary male infertility characterized by the production of a majority of round-headed spermatozoa without an acrosome (summary by Harbuz et al., 2011).
- Genetic Heterogeneity of Spermatogenic Failure
... Globozoospermia is a rare phenotype of primary male infertility characterized by the production of a majority of round-headed spermatozoa without an acrosome (summary by Harbuz et al., 2011). - Genetic Heterogeneity of Spermatogenic Failure For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Kilani et al. (2004) studied a consanguineous Jordanian family in which 5 infertile brothers had a complete form of globozoospermia, with 100% of spermatozoa having round heads. There were 5 additional sibs in the family, including 2 sisters ... Kilani et al. (2004) studied a consanguineous Jordanian family in which 5 infertile brothers had a complete form of globozoospermia, with 100% of spermatozoa having round heads. There were 5 additional sibs in the family, including 2 sisters and 3 brothers, who were naturally fertile and had 3 to 7 children each. Semen analysis in the 5 infertile brothers showed a median volume of 3.3 mL (range, 1 mL to 4 mL), median concentration of 22 x 10(6)/mL (range, 5 to 60 x 10(6)/mL), and median progressive motility of 30% (range, 7-60%). A total of 20 cycles of intracytoplasmic sperm injection (ICSI) were performed for the 5 infertile brothers, resulting in only 1 full-term pregnancy and 2 miscarriages. Using an indirect immunofluorescence technique to evaluate the acrosomal status of the spermatozoa in 3 fertile and 3 infertile brothers, Kilani et al. (2004) observed that on average, 66% of the spermatozoa from the 3 fertile brothers had acrosomes present, whereas no acrosomes were seen in the globozoospermic brothers. Koscinski et al. (2011) analyzed semen from an Algerian patient with globozoospermia and deletion of the DPY19L2 gene (613893.0001), and observed all stages of spermatogenesis with no obvious abnormality in earlier stages of germ cells. In contrast, no proacrosomal vesicles were observed in the round spermatids, yet they appeared correctly polarized: the polarization of the spermatid was indicated by the correct positioning of the chromatoid body observed in the elongating spermatids, in the area of the attachment of the flagellum to the spermatid nucleus. In addition, in 2 unrelated French patients with globozoospermia and deletion of the DPY19L2 gene, the authors observed elongating spermatids as well as spermatozoa that were comparable to those of the Algerian patient.
In a consanguineous Jordanian family originally studied by Kilani et al. (2004), in which 5 infertile brothers had complete globozoospermia mapping to chromosome 12, Koscinski et al. (2011) analyzed the candidate gene DPY19L2 and observed specific amplifications in ... In a consanguineous Jordanian family originally studied by Kilani et al. (2004), in which 5 infertile brothers had complete globozoospermia mapping to chromosome 12, Koscinski et al. (2011) analyzed the candidate gene DPY19L2 and observed specific amplifications in controls that were not seen in affected individuals, suggesting a large deletion of the whole gene. Further analysis revealed homozygosity for an approximately 200-kb deletion encompassing only the DPY19L2 gene (613893.0001) in the affected brothers; all 3 healthy brothers were homozygous wildtype. The DPY19L2 deletion was then screened in 24 globozoospermic patients from 20 unrelated families, and similar deletions of DPY19L2 were identified in 4 patients from 3 families. Koscinski et al. (2011) noted that, in contrast to globozoospermic patients with mutation in the SPATA16 gene (see SPFG6, 609856), patients with the DPY19L2 deletion presented with complete globozoospermia yet had normal or near-normal concentrations of sperm, suggesting that lack of DPY19L2 may disrupt only spermiogenesis and not germ cell proliferation and meiosis. Deletion of DPY19L2 was not detected in the homozygous state in 105 men of European origin or in 101 fertile Jordanian men. In 9 probands with globozoospermia mapping to 12q14.2 and in the globozoospermic brother of 1 of the probands, Harbuz et al. (2011) analyzed the candidate gene DPY19L2 and identified homozygosity for deletion of DPY19L2 in 8 of the patients, including the 2 affected brothers. Analysis of DPY19L2 in an additional 10 globozoospermic probands revealed 7 more patients with a homozygous deletion of DPY19L2. Of the 15 patients with the deletion, 12 were Tunisian in origin, 2 were Moroccan, and 1 was Algerian. PCR amplification of exons 1 and 11 of the DPY19L2 gene in 200 fertile North African men and 100 fertile European men indicated that none was homozygous for the DPY19L2 deletion.