A new mutation identified in SPATA16 in two globozoospermic patients
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The aim of this study is to identify potential genes involved in human globozoopsermia.
Nineteen globozoospermic patients (previously screened for DPY19L2 mutations with no causative mutation) were recruited in this study and screened for mutations in genes implicated in human globozoospermia SPATA16 and PICK1. Using the candidate gene approach and the determination of Spata16 partners by Glutathione S-transferase (GST) pull-down four genes were also selected and screened for mutations.
We identified a novel mutation of SPATA16: deletion of 22.6 Kb encompassing the first coding exon in two unrelated Tunisian patients who presented the same deletion breakpoints. The two patients shared the same haplotype, suggesting a possible ancestral founder effect for this new deletion. Four genes were selected using the candidate gene approach and the GST pull-down (GOPC, PICK1, AGFG1 and IRGC) and were screened for mutation, but no variation was identified.
The present study confirms the pathogenicity of the SPATA16 mutations. The fact that no variation was detected in the coding sequence of AFGF1, GOPC, PICK1 and IRGC does not mean that they are not involved in human globozoospermia. A larger globozoospermic cohort must be studied in order to accelerate the process of identifying new genes involved in such phenotypes. Until sufficient numbers of patients have been screened, AFGF1, GOPC, PICK1 and IRGC should still be considered as candidate genes.
KeywordsGlobozoospermia Linkage analysis SPATA16 GST pull-down Male infertility
We would like to thank James Turner for his critical reading of the manuscript. We are grateful to the Institute of Genetics and Molecular and Cellular Biology (IGBMC) platforms. The study was funded by Agence Nationale de la Recherche and l’Agence de BioMédecine. This work was supported by the French Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), the Ministère de l’Education Nationale et de l’Enseignement Supérieur et de la Recherche, the University of Strasbourg, the University Hospital of Strasbourg, the Agence Nationale pour la Recherche and the Agence de la BioMédecine.
Compliance with ethical standards
This study was approved by the local Ethical Committee (Comité de protection de la personne, CPP (CPP 09/40 - W AC-2008-438 1W DC-2009-I 002)) of Strasbourg University Hospital. For each case analysed, informed written consent was obtained according to the CPP recommendations.