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Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots

Elias Ellnati, Paul Kuentz, Claire Redin, Sara Jaber, Frauke Vanden Meerschaut UGent, Joelle Makarian, Isabelle Koscinski, Mohammad H Nasr-Esfahani, Aygul Demirol and Timur Gurgan, et al. (2012) HUMAN MOLECULAR GENETICS. 21(16). p.3695-3702
abstract
To date, mutations in two genes, SPATA16 and DPY19L2, have been identified as responsible for a severe teratozoospermia, namely globozoospermia. The two initial descriptions of the DPY19L2 deletion lead to a very different rate of occurrence of this mutation among globospermic patients. In order to better estimate the contribution of DPY19L2 in globozoospermia, we screened a larger cohort including 64 globozoospermic patients. Twenty of the new patients were homozygous for the DPY19L2 deletion, and 7 were compound heterozygous for both this deletion and a point mutation. We also identified four additional mutated patients. The final mutation load in our cohort is 66.7 (36 out of 54). Out of 36 mutated patients, 69.4 are homozygous deleted, 19.4 heterozygous composite and 11.1 showed a homozygous point mutation. The mechanism underlying the deletion is a non-allelic homologous recombination (NAHR) between the flanking low-copy repeats. Here, we characterized a total of nine breakpoints for the DPY19L2 NAHR-driven deletion that clustered in two recombination hotspots, both containing direct repeat elements (AluSq2 in hotspot 1, THE1B in hotspot 2). Globozoospermia can be considered as a new genomic disorder. This study confirms that DPY19L2 is the major gene responsible for globozoospermia and enlarges the spectrum of possible mutations in the gene. This is a major finding and should contribute to the development of an efficient molecular diagnosis strategy for globozoospermia.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
SPLICING SIGNALS, FERTILIZATION, FAMILIAL GLOBOZOOSPERMIA, MALE-INFERTILITY, ASSISTED OOCYTE ACTIVATION, GENOMIC DISORDERS, INTRACYTOPLASMIC SPERM INJECTION, PREGNANCY, ICSI, REARRANGEMENTS
journal title
HUMAN MOLECULAR GENETICS
Hum. Mol. Genet.
volume
21
issue
16
pages
3695 - 3702
Web of Science type
Article
Web of Science id
000306964700015
JCR category
GENETICS & HEREDITY
JCR impact factor
7.692 (2012)
JCR rank
13/161 (2012)
JCR quartile
1 (2012)
ISSN
0964-6906
DOI
10.1093/hmg/dds200
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3049209
handle
http://hdl.handle.net/1854/LU-3049209
date created
2012-11-08 12:54:13
date last changed
2012-11-08 13:02:18
@article{3049209,
  abstract     = {To date, mutations in two genes, SPATA16 and DPY19L2, have been identified as responsible for a severe teratozoospermia, namely globozoospermia. The two initial descriptions of the DPY19L2 deletion lead to a very different rate of occurrence of this mutation among globospermic patients. In order to better estimate the contribution of DPY19L2 in globozoospermia, we screened a larger cohort including 64 globozoospermic patients. Twenty of the new patients were homozygous for the DPY19L2 deletion, and 7 were compound heterozygous for both this deletion and a point mutation. We also identified four additional mutated patients. The final mutation load in our cohort is 66.7 (36 out of 54). Out of 36 mutated patients, 69.4 are homozygous deleted, 19.4 heterozygous composite and 11.1 showed a homozygous point mutation. The mechanism underlying the deletion is a non-allelic homologous recombination (NAHR) between the flanking low-copy repeats. Here, we characterized a total of nine breakpoints for the DPY19L2 NAHR-driven deletion that clustered in two recombination hotspots, both containing direct repeat elements (AluSq2 in hotspot 1, THE1B in hotspot 2). Globozoospermia can be considered as a new genomic disorder. This study confirms that DPY19L2 is the major gene responsible for globozoospermia and enlarges the spectrum of possible mutations in the gene. This is a major finding and should contribute to the development of an efficient molecular diagnosis strategy for globozoospermia.},
  author       = {Ellnati, Elias and Kuentz, Paul and Redin, Claire and Jaber, Sara and Vanden Meerschaut, Frauke and Makarian, Joelle and Koscinski, Isabelle and Nasr-Esfahani, Mohammad H and Demirol, Aygul and Gurgan, Timur and Louanjli, Noureddine and Iqbal, Naeem and Bisharah, Mazen and Carr{\'e} Pigeon, Fr{\'e}d{\'e}rique and Gourabi, H and De Briel, Dominique and Brugnon, Florence and Gitlin, Susan A and Grillo, Jean-Marc and Ghaedi, Kamran and Deemeh, Mohammad R and Tanhaei, Somayeh and Modarres, Parastoo and Heindryckx, Bj{\"o}rn and Benkhalifa, Moncef and Nikiforaki, Dimitra and Oehninger, Sergio C and De Sutter, Petra and Muller, Jean and Viville, St{\'e}phane},
  issn         = {0964-6906},
  journal      = {HUMAN MOLECULAR GENETICS},
  keyword      = {SPLICING SIGNALS,FERTILIZATION,FAMILIAL GLOBOZOOSPERMIA,MALE-INFERTILITY,ASSISTED OOCYTE ACTIVATION,GENOMIC DISORDERS,INTRACYTOPLASMIC SPERM INJECTION,PREGNANCY,ICSI,REARRANGEMENTS},
  language     = {eng},
  number       = {16},
  pages        = {3695--3702},
  title        = {Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots},
  url          = {http://dx.doi.org/10.1093/hmg/dds200},
  volume       = {21},
  year         = {2012},
}

Chicago
Ellnati, Elias, Paul Kuentz, Claire Redin, Sara Jaber, Frauke Vanden Meerschaut, Joelle Makarian, Isabelle Koscinski, et al. 2012. “Globozoospermia Is Mainly Due to DPY19L2 Deletion via Non-allelic Homologous Recombination Involving Two Recombination Hotspots.” Human Molecular Genetics 21 (16): 3695–3702.
APA
Ellnati, E., Kuentz, P., Redin, C., Jaber, S., Vanden Meerschaut, F., Makarian, J., Koscinski, I., et al. (2012). Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots. HUMAN MOLECULAR GENETICS, 21(16), 3695–3702.
Vancouver
1.
Ellnati E, Kuentz P, Redin C, Jaber S, Vanden Meerschaut F, Makarian J, et al. Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots. HUMAN MOLECULAR GENETICS. 2012;21(16):3695–702.
MLA
Ellnati, Elias, Paul Kuentz, Claire Redin, et al. “Globozoospermia Is Mainly Due to DPY19L2 Deletion via Non-allelic Homologous Recombination Involving Two Recombination Hotspots.” HUMAN MOLECULAR GENETICS 21.16 (2012): 3695–3702. Print.