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Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa

Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and i...

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Autores principales: Cazin, Caroline, Boumerdassi, Yasmine, Martinez, Guillaume, Fourati Ben Mustapha, Selima, Whitfield, Marjorie, Coutton, Charles, Thierry-Mieg, Nicolas, Di Pizio, Pierre, Rives, Nathalie, Arnoult, Christophe, Touré, Aminata, Ray, Pierre F., Zouari, Raoudha, Sifer, Christophe, Kherraf, Zine-Eddine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927044/
https://www.ncbi.nlm.nih.gov/pubmed/33671757
http://dx.doi.org/10.3390/ijms22042187
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author Cazin, Caroline
Boumerdassi, Yasmine
Martinez, Guillaume
Fourati Ben Mustapha, Selima
Whitfield, Marjorie
Coutton, Charles
Thierry-Mieg, Nicolas
Di Pizio, Pierre
Rives, Nathalie
Arnoult, Christophe
Touré, Aminata
Ray, Pierre F.
Zouari, Raoudha
Sifer, Christophe
Kherraf, Zine-Eddine
author_facet Cazin, Caroline
Boumerdassi, Yasmine
Martinez, Guillaume
Fourati Ben Mustapha, Selima
Whitfield, Marjorie
Coutton, Charles
Thierry-Mieg, Nicolas
Di Pizio, Pierre
Rives, Nathalie
Arnoult, Christophe
Touré, Aminata
Ray, Pierre F.
Zouari, Raoudha
Sifer, Christophe
Kherraf, Zine-Eddine
author_sort Cazin, Caroline
collection PubMed
description Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses.
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spelling pubmed-79270442021-03-04 Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa Cazin, Caroline Boumerdassi, Yasmine Martinez, Guillaume Fourati Ben Mustapha, Selima Whitfield, Marjorie Coutton, Charles Thierry-Mieg, Nicolas Di Pizio, Pierre Rives, Nathalie Arnoult, Christophe Touré, Aminata Ray, Pierre F. Zouari, Raoudha Sifer, Christophe Kherraf, Zine-Eddine Int J Mol Sci Article Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses. MDPI 2021-02-22 /pmc/articles/PMC7927044/ /pubmed/33671757 http://dx.doi.org/10.3390/ijms22042187 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cazin, Caroline
Boumerdassi, Yasmine
Martinez, Guillaume
Fourati Ben Mustapha, Selima
Whitfield, Marjorie
Coutton, Charles
Thierry-Mieg, Nicolas
Di Pizio, Pierre
Rives, Nathalie
Arnoult, Christophe
Touré, Aminata
Ray, Pierre F.
Zouari, Raoudha
Sifer, Christophe
Kherraf, Zine-Eddine
Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa
title Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa
title_full Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa
title_fullStr Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa
title_full_unstemmed Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa
title_short Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa
title_sort identification and characterization of the most common genetic variant responsible for acephalic spermatozoa syndrome in men originating from north africa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927044/
https://www.ncbi.nlm.nih.gov/pubmed/33671757
http://dx.doi.org/10.3390/ijms22042187
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