Genome-wide compound heterozygote analysis highlights DPY19L2 alleles in a non-consanguineous Spanish family with a complete form of globozoospermia
Research question: Would the use of genome-wide genotyping be an advantageous strategy to identify the molecular aetiology of two brothers from a non-consanguineous family, clinically diagnosed with total globozoospermia? Design: Two related Spanish globozoospermic patients were studied. Eight first...
| Authors: | , , , , |
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| Format: | article |
| Status: | Versión aceptada para publicación |
| Publication Date: | 2022 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/186215 |
| Online Access: | https://hdl.handle.net/2445/186215 |
| Access Level: | Open access |
| Keyword: | Esterilitat masculina Genètica Male sterility Genetics |
| Summary: | Research question: Would the use of genome-wide genotyping be an advantageous strategy to identify the molecular aetiology of two brothers from a non-consanguineous family, clinically diagnosed with total globozoospermia? Design: Two related Spanish globozoospermic patients were studied. Eight first- and second-degree family members were also included in the study. The clinical procedure included anamnesis, physical examination and semen analyses. Acrosome visualization was performed by fluorescein isothiocyanate-Pisum sativum agglutinin labelling and ultrastructural electron microscope sperm analysis. Sperm DNA fragmentation was determined by TUNEL and SCD. Molecular analysis included: the detection of deletion of the DPY19L2 gene by a BPa (break point "a") gap-polymerase chain reaction, and genotyping by using a high-throughput genome-wide genotyping platform and a genotype imputation strategy. Results: The biological characteristics of the two globozoospermic siblings included round-headed spermatozoa without an acrosome; ultrastructural defects in spermatozoa; increased sperm fragmentation and aneuploidies, inability of spermatozoa to activate oocytes (correctable with artificial activation) and good developmental potential of embryos generated by IVF/intracytoplasmic sperm injection. This genetic study focused on a genome-wide compound heterozygote analysis that identified two deleterious rare coding variants in the DPY19L2 gene [rs771726551 (c.431T>A exon 3) and rs147579680 (c.869G>A exon 8)]. Conclusion: A genome-wide compound heterozygote analysis strategy should be considered for molecular screening in globozoospermia and other rare congenital diseases, particularly in cases from non-consanguineous families. |
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