PMID- 26516168
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20220330
IS  - 1460-2407 (Electronic)
IS  - 1360-9947 (Linking)
VI  - 22
IP  - 1
DP  - 2016 Jan
TI  - Identification of a new DPY19L2 mutation and a better definition of DPY19L2 
      deletion breakpoints leading to globozoospermia.
PG  - 35-45
LID - 10.1093/molehr/gav061 [doi]
AB  - STUDY HYPOTHESIS: The purpose of this study was to analyze DPY19L2 sequence 
      variants to investigate the mechanism leading to the entire DPY19L2 deletion in a 
      large cohort of infertile globozoospermic patients. STUDY FINDING: An improved 
      analysis of the DPY19L2 deletion breakpoints (BPs) allowed us to identify two BPs 
      located in a small 1 kb region and to more precisely localize the BPs reported 
      previously. WHAT IS KNOWN ALREADY: Three genes [spermatogenesis associated 16 
      (SPATA16), protein interacting with PRKCA (PICK1) and DPY19L2] were previously 
      correlated with globozoospermia, but a homozygous deletion of the entire DPY19L2 
      was identified as the most frequent alteration causing this phenotype. In 
      addition, several point mutations in this gene were reported. In previous work, 
      we have identified nine BPs for the DPY19L2 deletion clustered in two hotspot 
      regions, while others reported a total of five BPs. STUDY DESIGN, 
      SAMPLES/MATERIALS, METHODS: We screened for the DPY19L2 deletion and for 
      mutations in the DPY19L2, SPATA16 and PICK1 genes in a cohort of 21 Tunisian 
      globozoospermic patients. In order to characterize the DPY19L2 deletion BPs, we 
      sequenced a 2 kb fragment on low copy repeat (LCR) 1 and LCR2 in Tunisian fertile 
      controls to distinguish between single-nucleotide polymorphisms (SNPs) and 
      LCR-specific markers. MAIN RESULTS AND THE ROLE OF CHANCE: Molecular analyses 
      performed on 18 genetically independent individuals showed that 11 (61.1%) were 
      homozygous for the DPY19L2 deletion, 2 (11.1%) were homozygous for the 
      non-synonymous mutation (p.R298C) in exon 8, 1 patient (5.6%) was homozygous for 
      a new splice-site mutation at the junction exon-intron 16 
      [c.1579_1580+4delAGGTAAinsTCAT] and no DPY19L2, SPATA16 or PICK1 mutations were 
      identified for 4 patients (22.2%). By defining 15 specific LCR markers, we 
      characterized 2 BPs for the DPY19L2 deletion in 11 patients showing the 
      homozygous deletion. Using 20 non-LCR-specific SNPs, we identified 8 distinct 
      haplotypes. LIMITATIONS, REASONS FOR CAUTION: A limitation of this study is the 
      small number of patients owing to the rarity of this form of male infertility. 
      WIDER IMPLICATIONS OF THE FINDINGS: Our data showed that some nucleotides, 
      described by others as LCR-specific markers and used to limit their BPs, were in 
      fact SNPs demonstrating the difficulty in precisely determining the localization 
      of BPs. LARGE SCALE DATA: Not applicable. STUDY FUNDING AND COMPETING INTERESTS: 
      This work was supported by the French Centre National de la Recherche 
      Scientifique (CNRS), Institut National de la Sante et de la Recherche Medicale 
      (INSERM), the Ministere de l'Education Nationale et de l'Enseignement Superieur 
      et de la Recherche, the University of Strasbourg, the University Hospital of 
      Strasbourg, the Agence Nationale pour la Recherche, the Agence de la BioMedecine 
      and l'Agence Universitaire de la Francophonie (AUF). There are no conflicts of 
      interest to declare.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the European 
      Society of Human Reproduction and Embryology. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Ghedir, Houda
AU  - Ghedir H
AD  - Laboratoire de Cytogenetique, Genetique Moleculaire et Biologie de la 
      Reproduction Humaines, CHU Farhat Hached, 4000 Sousse, Tunisia.
FAU - Ibala-Romdhane, Samira
AU  - Ibala-Romdhane S
AD  - Laboratoire de Cytogenetique, Genetique Moleculaire et Biologie de la 
      Reproduction Humaines, CHU Farhat Hached, 4000 Sousse, Tunisia.
FAU - Okutman, Ozlem
AU  - Okutman O
AD  - Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Institut 
      National de Sante et de Recherche Medicale INSERM U964, Centre National de 
      Recherche scientifique CNRS UMR 1704, Universite de Strasbourg, Illkirch 67404, 
      France Centre Hospitalier Universitaire, Strasbourg F-67000, France.
FAU - Viot, Geraldine
AU  - Viot G
AD  - Unite de Genetique Medicale, Maternite Port-Royal, Hopital Cochin, 75679 Paris 
      14, France.
FAU - Saad, Ali
AU  - Saad A
AD  - Laboratoire de Cytogenetique, Genetique Moleculaire et Biologie de la 
      Reproduction Humaines, CHU Farhat Hached, 4000 Sousse, Tunisia.
FAU - Viville, Stephane
AU  - Viville S
AD  - Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Institut 
      National de Sante et de Recherche Medicale INSERM U964, Centre National de 
      Recherche scientifique CNRS UMR 1704, Universite de Strasbourg, Illkirch 67404, 
      France Centre Hospitalier Universitaire, Strasbourg F-67000, France 
      viville@igbmc.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151029
PL  - England
TA  - Mol Hum Reprod
JT  - Molecular human reproduction
JID - 9513710
RN  - 0 (Carrier Proteins)
RN  - 0 (DPY19L2 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PICk1 protein, human)
RN  - 0 (RNA Splice Sites)
RN  - 0 (SPATA16 protein, human)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Acrosome/ultrastructure
MH  - Alleles
MH  - Carrier Proteins/genetics
MH  - Chromosome Breakpoints
MH  - Consanguinity
MH  - Exons/genetics
MH  - Gene Deletion
MH  - Gene Dosage
MH  - Haplotypes/genetics
MH  - Homeodomain Proteins/genetics
MH  - Humans
MH  - Infertility, Male/*genetics
MH  - Male
MH  - Membrane Proteins/deficiency/*genetics/physiology
MH  - Nuclear Proteins/genetics
MH  - Point Mutation
MH  - Polymorphism, Single Nucleotide
MH  - RNA Splice Sites/genetics
MH  - Sequence Alignment
MH  - Spermatozoa/abnormalities/ultrastructure
MH  - Tunisia/epidemiology
MH  - Vesicular Transport Proteins
OTO - NOTNLM
OT  - DPY19L2
OT  - breakpoints
OT  - globozoospermia
OT  - male infertility
OT  - non-allelic homologous recombination
OT  - round-headed
EDAT- 2015/10/31 06:00
MHDA- 2016/10/07 06:00
CRDT- 2015/10/31 06:00
PHST- 2015/08/18 00:00 [received]
PHST- 2015/10/20 00:00 [accepted]
PHST- 2015/10/31 06:00 [entrez]
PHST- 2015/10/31 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
AID - gav061 [pii]
AID - 10.1093/molehr/gav061 [doi]
PST - ppublish
SO  - Mol Hum Reprod. 2016 Jan;22(1):35-45. doi: 10.1093/molehr/gav061. Epub 2015 Oct 
      29.