Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity

Sean Brown, Melissa Miller, Polina V. Lishko, Douglas Lester, Stephen Publicover, Christopher Barratt, Sarah Martins da Silva

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Study question: Does a man (patient 1) with a previously described deficiency in CatSper channel function have a mutation in CATSPERE and/or CATSPERZ?

Summary answer: Patient 1 possess a homozygous in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE.

What is known already: CatSper is the principal calcium channel of mammalian spermatozoa. Spermatozoa from patient 1 had a specific loss of CatSper function and were unable to fertilise at in vitro fertilization (IVF). Loss of CatSper function could not be attributed to genetic abnormalities in coding regions of seven CatSper subunits (Williams et al., 2015). Two additional subunits (CatSper-epsilon (CATPSERE) and CatSper-zeta (CATSPERZ) were recently identified (Chung et al., 2017), and are now proposed to contribute to the formation of the mature channel complex.

Study design, size, duration: This was a basic medical research study analyzing genomic data from a single patient (patient 1) for defects in CATSPERE and CATSPERZ.

Participants/materials, setting, methods: The original exome sequencing data for patient 1 was analysed for mutations in CATSPERE and CATSPERZ. Sanger sequencing was conducted to confirm the presence of a rare variant.

Main results and the role of chance: Patient 1 is homozygous for an in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE that is predicted to be highly deleterious.

Limitations, reasons for caution: The nature of the molecular deficit caused by the rs761237686 variant and whether it is exclusively responsible for the loss of CatSper function remain to be elucidated.

Wider implications of the findings: Population genetics are available for a significant number of predicted deleterious variants of CatSper subunits. The consequence of homozygous and compound heterozygous forms on sperm fertilisation potential could be significant. Selective targeting of CatSper subunit expression maybe a feasible strategy for the development of novel contraceptives.

Study funding/competing interest(s): This study was funded by project grants from the MRC (MR/K013343/1, MR/012492/1), Chief Scientist Office/NHS research Scotland. This work was also supported by NIH R01GM111802, Pew Biomedical Scholars Award 00028642 and Packer Wentz Endowment Will to P.V.L.
Original languageEnglish
Pages (from-to)1812–1816
Number of pages5
JournalHuman Reproduction
Issue number10
Early online date18 Sept 2018
Publication statusPublished - 1 Oct 2018


  • Calcium signaling
  • infertility
  • CatSper
  • spermatozoa
  • mutation


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