Ghent University Academic Bibliography

Advanced

A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility

Junaid Kashir, Michalis Konstantinidis, Celine Jones, Bernadette Lemmon, Hoi Chang Lee, Rebecca Hamer, Björn Heindryckx UGent, Charlotte M Deane, Petra De Sutter UGent and Rafael A Fissore, et al. (2012) HUMAN REPRODUCTION. 27(1). p.222-231
abstract
BACKGROUND: Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLC zeta). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLC zeta(H398P)), leading to abnormal PLC zeta function and infertility. METHODS AND RESULTS: Here, using a combination of direct-sequencing and mini-sequencing of the PLC zeta gene from the patient and his family, we report the identification of a second PLC zeta mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLC zeta(H233L)), which is predicted to disrupt local protein interactions in a manner similar to PLC zeta(H398P) and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLC zeta(H233L) and PLC zeta(H398P) exist on distinct parental chromosomes, the former inherited from the patient's mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency. CONCLUSIONS: Collectively, our findings provide further evidence regarding the importance of PLC zeta at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms.
Please use this url to cite or link to this publication:
author
organization
alternative title
A maternally inherited autosomal point mutation in human phospholipase C zeta (PLC zeta) leads to male infertility
year
type
journalArticle (original)
publication status
published
subject
keyword
TRANSCRIPTION, LOCALIZATION, CALCIUM, FERTILIZATION, SPERM, OOCYTE ACTIVATION, EGG ACTIVATION, EMBRYO DEVELOPMENT, TRIGGERS CA2+ OSCILLATIONS, inheritance, infertility, oocyte activation, sperm, phophospholipase C zeta (PLCzeta), ROUND-HEADED SPERMATOZOA
journal title
HUMAN REPRODUCTION
Hum. Reprod.
volume
27
issue
1
pages
222 - 231
Web of Science type
Article
Web of Science id
000299220600029
JCR category
OBSTETRICS & GYNECOLOGY
JCR impact factor
4.67 (2012)
JCR rank
3/77 (2012)
JCR quartile
1 (2012)
ISSN
0268-1161
DOI
10.1093/humrep/der384
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2049007
handle
http://hdl.handle.net/1854/LU-2049007
date created
2012-02-28 13:44:44
date last changed
2012-03-08 16:47:52
@article{2049007,
  abstract     = {BACKGROUND: Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLC zeta). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLC zeta(H398P)), leading to abnormal PLC zeta function and infertility. 
METHODS AND RESULTS: Here, using a combination of direct-sequencing and mini-sequencing of the PLC zeta gene from the patient and his family, we report the identification of a second PLC zeta mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLC zeta(H233L)), which is predicted to disrupt local protein interactions in a manner similar to PLC zeta(H398P) and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLC zeta(H233L) and PLC zeta(H398P) exist on distinct parental chromosomes, the former inherited from the patient's mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency. 
CONCLUSIONS: Collectively, our findings provide further evidence regarding the importance of PLC zeta at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms.},
  author       = {Kashir, Junaid and Konstantinidis, Michalis and Jones, Celine and Lemmon, Bernadette and Lee, Hoi Chang and Hamer, Rebecca and Heindryckx, Bj{\"o}rn and Deane, Charlotte M and De Sutter, Petra and Fissore, Rafael A and Parrington, John and Wells, Dagan and Coward, Kevin},
  issn         = {0268-1161},
  journal      = {HUMAN REPRODUCTION},
  keyword      = {TRANSCRIPTION,LOCALIZATION,CALCIUM,FERTILIZATION,SPERM,OOCYTE ACTIVATION,EGG ACTIVATION,EMBRYO DEVELOPMENT,TRIGGERS CA2+ OSCILLATIONS,inheritance,infertility,oocyte activation,sperm,phophospholipase C zeta (PLCzeta),ROUND-HEADED SPERMATOZOA},
  language     = {eng},
  number       = {1},
  pages        = {222--231},
  title        = {A maternally inherited autosomal point mutation in human phospholipase C zeta (PLC\ensuremath{\zeta}) leads to male infertility},
  url          = {http://dx.doi.org/10.1093/humrep/der384},
  volume       = {27},
  year         = {2012},
}

Chicago
Kashir, Junaid, Michalis Konstantinidis, Celine Jones, Bernadette Lemmon, Hoi Chang Lee, Rebecca Hamer, Björn Heindryckx, et al. 2012. “A Maternally Inherited Autosomal Point Mutation in Human Phospholipase C Zeta (PLCζ) Leads to Male Infertility.” Human Reproduction 27 (1): 222–231.
APA
Kashir, Junaid, Konstantinidis, M., Jones, C., Lemmon, B., Lee, H. C., Hamer, R., Heindryckx, B., et al. (2012). A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility. HUMAN REPRODUCTION, 27(1), 222–231.
Vancouver
1.
Kashir J, Konstantinidis M, Jones C, Lemmon B, Lee HC, Hamer R, et al. A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility. HUMAN REPRODUCTION. 2012;27(1):222–31.
MLA
Kashir, Junaid, Michalis Konstantinidis, Celine Jones, et al. “A Maternally Inherited Autosomal Point Mutation in Human Phospholipase C Zeta (PLCζ) Leads to Male Infertility.” HUMAN REPRODUCTION 27.1 (2012): 222–231. Print.