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A new mutation identified in SPATA16 in two globozoospermic patients

  • Elias ElInati
  • Camille Fossard
  • Ozlem Okutman
  • Houda Ghédir
  • Samira Ibala-Romdhane
  • Pierre F. Ray
  • Ali Saad
  • Sylvianne Hennebicq
  • Stéphane Viville
Genetics

Abstract

Purpose

The aim of this study is to identify potential genes involved in human globozoopsermia.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Globozoospermia Linkage analysis SPATA16 GST pull-down Male infertility 

Notes

Acknowledgements

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.

Supplementary material

10815_2016_715_MOESM1_ESM.docx (18 kb)
Table S.1 (DOCX 18 kb)
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Table S.2 (DOCX 24 kb)
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Table S.3 (DOCX 23 kb)
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Table S.4 (DOCX 27 kb)
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Table S.5 (DOCX 17 kb)
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Figure 1

GST pull-down. GST-SPATA16 fusion protein (lane 1) and control GST protein (lane 2) were subjected to pull-down reaction in the presence of cell extract derived from adult mice testes. The samples were fractionated in SDS-PAGE and stained with silver. (GIF 75 kb)

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High Resolution image (TIF 15722 kb)
10815_2016_715_Fig3_ESM.gif (59 kb)
Figure 2

Linkage analysis. (A) SNP array results revealing a unique homozygous region shared between the brothers of the three families. The genes located in the region of 4.7 Mb on the chromosome eight are represented in the table below it. (B) SNP array results showing the two brothers of family B sharing a homozygous region for IRGC locus (loc.chr19: 43,716,010 – 43,720,021). (GIF 58 kb)

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High Resolution image (TIF 3525 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Elias ElInati
    • 1
    • 2
  • Camille Fossard
    • 1
  • Ozlem Okutman
    • 1
    • 3
  • Houda Ghédir
    • 4
  • Samira Ibala-Romdhane
    • 4
  • Pierre F. Ray
    • 5
    • 6
    • 7
    • 8
    • 9
  • Ali Saad
    • 4
  • Sylvianne Hennebicq
    • 5
    • 6
    • 7
    • 8
    • 9
  • Stéphane Viville
    • 1
    • 3
  1. 1.Département Génomique Fonctionnelle et Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de StrasbourgIllkirchFrance
  2. 2.The Francis Crick Institute, Mill Hill LaboratoryLondonUK
  3. 3.Centre Hospitalier Universitaire de StrasbourgStrasbourgFrance
  4. 4.Laboratoire de CytogénétiqueGénétique Moléculaire et Biologie de la Reproduction Humaines. CHU Farhat HachedSousseTunisie
  5. 5.Université Grenoble AlpesGrenobleFrance
  6. 6.Equipe “Génétique, Epigénétique et thérapies de l’Infertilité” Institut Albert Bonniot, INSERM U823GrenobleFrance
  7. 7.CHU de Grenoble, UF de Biochimie et Génétique MoléculaireGrenobleFrance
  8. 8.Fédération Française des CECOSParisFrance
  9. 9.Faculté de Médecine de GrenobleLaboratoire d’Aide à la Procréation-CECOS, Laboratoire AGe, Imagerie, Modélisation, Équipe Génétique-Infertilité-ThérapeutiqueGrenobleFrance

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