Imperial College London
Alternate

Dr. Channa Jayasena MA PhD MRCP FRCPath

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Reader in Reproductive Endocrinology
 
 
 
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Contact

 

c.jayasena Website

 
 
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Location

 

6N5CCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wyrwoll:2022:10.1016/j.ajhg.2022.09.002,
author = {Wyrwoll, MJ and Gaasbeek, CM and Golubickaite, I and Stakaitis, R and Oud, MS and Nagirnaja, L and Dion, C and Sindi, EB and Leitch, HG and Jayasena, CN and Sironen, A and Dicke, A-K and Rotte, N and Stallmeyer, B and Kliesch, S and Grangeiro, CHP and Araujo, TF and Lasko, P and Genetics, of Male Infertility Initiative GEMINI consortium and D'Hauwers, K and Smits, RM and Ramos, L and Xavier, MJ and Conrad, DF and Almstrup, K and Veltman, JA and Tüttelmann, F and van, der Heijden GW},
doi = {10.1016/j.ajhg.2022.09.002},
journal = {American Journal of Human Genetics},
pages = {1850--1866},
title = {The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans},
url = {http://dx.doi.org/10.1016/j.ajhg.2022.09.002},
volume = {109},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Infertility affects around 7% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with SPGF and detected rare bi-allelic loss-of-function variants in FKBP6 in five additional persons. All six individuals had no or extremely few sperm in the ejaculate, which were not suitable for medically assisted reproduction. Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining. In mice, Fkbp6 is essential for spermatogenesis and has been described as being involved in piRNA biogenesis and formation of the synaptonemal complex (SC). We did not detect FKBP6 as part of the SC in normal human spermatocytes, but small RNA sequencing revealed that loss of FKBP6 severely impacted piRNA levels, supporting a role for FKBP6 in piRNA biogenesis in humans. In contrast to findings in piRNA-pathway mouse models, we did not detect an increase in LINE-1 expression in men with pathogenic FKBP6 variants. Based on our findings, FKBP6 reaches a "strong" level of evidence for being associated with male infertility according to the ClinGen criteria, making it directly applicable for clinical diagnostics. This will improve patient care by providing a causal diagnosis and will help to predict chances for successful surgical sperm retrieval.
AU  - Wyrwoll,MJ
AU  - Gaasbeek,CM
AU  - Golubickaite,I
AU  - Stakaitis,R
AU  - Oud,MS
AU  - Nagirnaja,L
AU  - Dion,C
AU  - Sindi,EB
AU  - Leitch,HG
AU  - Jayasena,CN
AU  - Sironen,A
AU  - Dicke,A-K
AU  - Rotte,N
AU  - Stallmeyer,B
AU  - Kliesch,S
AU  - Grangeiro,CHP
AU  - Araujo,TF
AU  - Lasko,P
AU  - Genetics,of Male Infertility Initiative GEMINI consortium
AU  - D'Hauwers,K
AU  - Smits,RM
AU  - Ramos,L
AU  - Xavier,MJ
AU  - Conrad,DF
AU  - Almstrup,K
AU  - Veltman,JA
AU  - Tüttelmann,F
AU  - van,der Heijden GW
DO  - 10.1016/j.ajhg.2022.09.002
EP  - 1866
PY  - 2022///
SN  - 0002-9297
SP  - 1850
TI  - The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans
T2  - American Journal of Human Genetics
UR  - http://dx.doi.org/10.1016/j.ajhg.2022.09.002
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36150389
UR  - http://hdl.handle.net/10044/1/100063
VL  - 109
ER  -
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