Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient

BACKGROUND: Ubiquitin‐Specific Peptidase 26 (USP26), located on the X chromosome, encodes a deubiquitinating enzyme expressed mainly in testis, where it regulates protein turnover during spermatogenesis and modulates the ubiquitination levels of the Androgen Receptor (AR), and as a consequence, affe...

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Autores principales: Arafat, Maram, Zeadna, Atif, Levitas, Eliahu, Har Vardi, Iris, Samueli, Benzion, Shaco‐Levy, Ruth, Dabsan, Salam, Lunenfeld, Eitan, Huleihel, Mahmoud, Parvari, Ruti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336752/
https://www.ncbi.nlm.nih.gov/pubmed/32410375
http://dx.doi.org/10.1002/mgg3.1258
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author Arafat, Maram
Zeadna, Atif
Levitas, Eliahu
Har Vardi, Iris
Samueli, Benzion
Shaco‐Levy, Ruth
Dabsan, Salam
Lunenfeld, Eitan
Huleihel, Mahmoud
Parvari, Ruti
author_facet Arafat, Maram
Zeadna, Atif
Levitas, Eliahu
Har Vardi, Iris
Samueli, Benzion
Shaco‐Levy, Ruth
Dabsan, Salam
Lunenfeld, Eitan
Huleihel, Mahmoud
Parvari, Ruti
author_sort Arafat, Maram
collection PubMed
description BACKGROUND: Ubiquitin‐Specific Peptidase 26 (USP26), located on the X chromosome, encodes a deubiquitinating enzyme expressed mainly in testis, where it regulates protein turnover during spermatogenesis and modulates the ubiquitination levels of the Androgen Receptor (AR), and as a consequence, affects AR signaling. METHODS: The patient was thoroughly characterized clinically. He was genetically tested by chromosome analysis and whole exome sequencing (WES). RESULTS: The patient was diagnosed with Sertoli cell‐only syndrome pattern (SCOS). The WES analysis revealed only the variation in USP26: causing p.P469S in a highly evolutionary conserved amino acid as the possible cause for SCOS. The literature search identified 34 single variations and 14 clusters of variations in USP26 that were associated with male infertility. Only one of the 22 variations and of one cluster of three mutations tested for ubiquitination activity was found as damaging. Only one out of six variations tested for effect on AR function was found as damaging. Thus, the association of USP26 with male fertility was questioned. CONCLUSIONS: The finding in our patient and the discussion on the reviewed literature support a possible role for USP26 in male fertility.
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spelling pubmed-73367522020-07-08 Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient Arafat, Maram Zeadna, Atif Levitas, Eliahu Har Vardi, Iris Samueli, Benzion Shaco‐Levy, Ruth Dabsan, Salam Lunenfeld, Eitan Huleihel, Mahmoud Parvari, Ruti Mol Genet Genomic Med Clinical Reports BACKGROUND: Ubiquitin‐Specific Peptidase 26 (USP26), located on the X chromosome, encodes a deubiquitinating enzyme expressed mainly in testis, where it regulates protein turnover during spermatogenesis and modulates the ubiquitination levels of the Androgen Receptor (AR), and as a consequence, affects AR signaling. METHODS: The patient was thoroughly characterized clinically. He was genetically tested by chromosome analysis and whole exome sequencing (WES). RESULTS: The patient was diagnosed with Sertoli cell‐only syndrome pattern (SCOS). The WES analysis revealed only the variation in USP26: causing p.P469S in a highly evolutionary conserved amino acid as the possible cause for SCOS. The literature search identified 34 single variations and 14 clusters of variations in USP26 that were associated with male infertility. Only one of the 22 variations and of one cluster of three mutations tested for ubiquitination activity was found as damaging. Only one out of six variations tested for effect on AR function was found as damaging. Thus, the association of USP26 with male fertility was questioned. CONCLUSIONS: The finding in our patient and the discussion on the reviewed literature support a possible role for USP26 in male fertility. John Wiley and Sons Inc. 2020-05-15 /pmc/articles/PMC7336752/ /pubmed/32410375 http://dx.doi.org/10.1002/mgg3.1258 Text en © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Clinical Reports
Arafat, Maram
Zeadna, Atif
Levitas, Eliahu
Har Vardi, Iris
Samueli, Benzion
Shaco‐Levy, Ruth
Dabsan, Salam
Lunenfeld, Eitan
Huleihel, Mahmoud
Parvari, Ruti
Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient
title Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient
title_full Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient
title_fullStr Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient
title_full_unstemmed Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient
title_short Novel mutation in USP26 associated with azoospermia in a Sertoli cell‐only syndrome patient
title_sort novel mutation in usp26 associated with azoospermia in a sertoli cell‐only syndrome patient
topic Clinical Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336752/
https://www.ncbi.nlm.nih.gov/pubmed/32410375
http://dx.doi.org/10.1002/mgg3.1258
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