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AURKC<\/jats:styled-content><\/jats:italic> was sequenced in case of sperm macrocephaly while the DPY<\/jats:styled-content>19L2<\/jats:italic> status has been analyzed by multiple approaches including a novel qPCR<\/jats:styled-content>\u2013based copy number assay in case of globozoospermia. Globozoospermic patients were also analyzed for SPACA<\/jats:styled-content>1<\/jats:italic>, a novel candidate gene herein tested for the first time in humans. The effect of the patients\u2019 genetic status was interrogated by implementing the molecular screening with the characterization of several sperm parameters: (i) routine sperm analysis, integrated with transmission electron microscopy; (ii) sperm fluorescent in situ hybridization (FISH<\/jats:styled-content>) analysis; (iii) sperm DNA<\/jats:styled-content> fragmentation (DF<\/jats:styled-content>) analysis. Moreover, for the first time, we performed microsatellite instability analysis as a marker of genome instability in men with sperm macrocephaly and globozoospermia. Finally, artificial reproductive technology (ART<\/jats:styled-content>) history has been reported for those patients who underwent the treatment. Macrocephalic patients had an AURKC<\/jats:styled-content><\/jats:italic> mutation and >89% tetraploid, highly fragmented spermatozoa. DPY<\/jats:styled-content>19L2<\/jats:italic> was mutated in all patients with >80% globozoospermia: the two homozygous deleted men and the compound heterozygous showed the severest phenotype (90\u2013100%). The newly developed qPCR<\/jats:styled-content> method was fully validated and has the potential of detecting also yet undiscovered deletions. DPY<\/jats:styled-content>19L2<\/jats:italic> status is unlikely related to FISH<\/jats:styled-content> anomalies and DF<\/jats:styled-content>, although globozoospermic men showed a higher disomy rate and DF<\/jats:styled-content> compared with internal reference values. No patient was mutated for SPACA<\/jats:styled-content>1<\/jats:italic>. Our data support the general agreement on the negative correlation between macro\/globozoospermia and conventional intracytoplasmic sperm injection outcomes. Microsatellites were stable in all patients analyzed. The comprehensive picture provided on these severe phenotypes causing infertility is of relevance in the management of patients undergoing ART.<\/jats:p>","DOI":"10.1111\/andr.12016","type":"journal-article","created":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T17:43:38Z","timestamp":1425663818000},"page":"203-212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Comprehensive investigation in patients affected by sperm macrocephaly and globozoospermia"],"prefix":"10.1111","volume":"3","author":[{"given":"C.","family":"Chianese","sequence":"first","affiliation":[{"name":"Sexual Medicine and andrology Unit Department of Experimental and Clinical Biomedical Sciences \u2018Mario Serio\u2019 University of Florence and Centre of Excellence DeNothe Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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