Biallelic variant in cyclin B3 is associated with failure of maternal meiosis II and recurrent digynic triploidy.
copy-number
reproductive medicine
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
11
02
2020
revised:
07
07
2020
accepted:
27
07
2020
pubmed:
18
9
2020
medline:
22
2
2022
entrez:
17
9
2020
Statut:
ppublish
Résumé
Triploidy is one of the most common chromosome abnormalities affecting human gestation and accounts for an important fraction of first-trimester miscarriages. Triploidy has been demonstrated in a few cases of recurrent pregnancy loss (RPL) but its molecular mechanisms are unknown. This study aims to identify the genetic cause of RPL associated with fetus triploidy. We investigated genomic imprinting, genotyped sequence-tagged site (STS) markers and performed exome sequencing in a family including two sisters with RPL. Moreover, we evaluated oocyte maturation in vivo and in vitro and effect of the candidate protein variant in silico. While features of hydatidiform mole were excluded, the presence of triploidy of maternal origin was demonstrated in the fetuses. Oocyte maturation was deficient and all the maternally inherited pericentromeric STS alleles were homozygous in the fetuses. A deleterious missense variant (p.V1251D) of the cyclin B3 gene ( Here, we report a family in which a damaging variant in cyclin B3 is associated with the failure of oocyte meiosis II and recurrent fetus triploidy, implicating a rationale for
Sections du résumé
BACKGROUND
Triploidy is one of the most common chromosome abnormalities affecting human gestation and accounts for an important fraction of first-trimester miscarriages. Triploidy has been demonstrated in a few cases of recurrent pregnancy loss (RPL) but its molecular mechanisms are unknown. This study aims to identify the genetic cause of RPL associated with fetus triploidy.
METHODS
We investigated genomic imprinting, genotyped sequence-tagged site (STS) markers and performed exome sequencing in a family including two sisters with RPL. Moreover, we evaluated oocyte maturation in vivo and in vitro and effect of the candidate protein variant in silico.
RESULTS
While features of hydatidiform mole were excluded, the presence of triploidy of maternal origin was demonstrated in the fetuses. Oocyte maturation was deficient and all the maternally inherited pericentromeric STS alleles were homozygous in the fetuses. A deleterious missense variant (p.V1251D) of the cyclin B3 gene (
CONCLUSION
Here, we report a family in which a damaging variant in cyclin B3 is associated with the failure of oocyte meiosis II and recurrent fetus triploidy, implicating a rationale for
Identifiants
pubmed: 32938693
pii: jmedgenet-2020-106909
doi: 10.1136/jmedgenet-2020-106909
pmc: PMC8551973
doi:
Substances chimiques
CCNB3 protein, human
0
Cyclin B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
783-788Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Prenat Diagn. 2000 Jul;20(7):561-3
pubmed: 10913954
Biochem Biophys Res Commun. 2020 Jan 1;521(1):265-269
pubmed: 31640856
Genes Chromosomes Cancer. 2017 Dec;56(12):832-840
pubmed: 28730668
Fertil Steril. 2000 Dec;74(6):1153-8
pubmed: 11119743
Cell Cycle. 2007 Jun 1;6(11):1350-9
pubmed: 17495531
J Cell Biol. 2019 May 6;218(5):1553-1563
pubmed: 30770433
J Cell Biol. 2019 Apr 1;218(4):1265-1281
pubmed: 30723090
Cytogenet Genome Res. 2017;152(2):81-89
pubmed: 28662500
Cell Cycle. 2008 Nov 15;7(22):3509-13
pubmed: 19001847
Int J Dev Biol. 2008;52(5-6):449-54
pubmed: 18649257
Turk J Obstet Gynecol. 2018 Jun;15(2):112-125
pubmed: 29971189
Biochem Biophys Res Commun. 2002 Feb 22;291(2):406-13
pubmed: 11846420
J Endocrinol Invest. 2020 Sep;43(9):1271-1281
pubmed: 32166698
Nucleic Acids Res. 2018 Jul 2;46(W1):W350-W355
pubmed: 29718330
Mol Cytogenet. 2011 May 09;4:12
pubmed: 21549014
Clin Obstet Gynecol. 2007 Mar;50(1):132-45
pubmed: 17304030
Hum Reprod Update. 2002 Sep-Oct;8(5):463-81
pubmed: 12398226
PLoS One. 2014 May 12;9(5):e96818
pubmed: 24820964
PLoS Genet. 2010 Nov 24;6(11):e1001218
pubmed: 21124864
EMBO J. 1994 Feb 1;13(3):595-605
pubmed: 8313904
Mod Pathol. 2018 Jul;31(7):1116-1130
pubmed: 29463882
Nat Genet. 2012 Mar 04;44(4):461-6
pubmed: 22387997
Clin Genet. 2000 Sep;58(3):192-200
pubmed: 11076041
Cell Cycle. 2019 Jul;18(14):1537-1548
pubmed: 31208271
BMC Evol Biol. 2011 Jul 28;11:224
pubmed: 21798004
Semin Reprod Med. 2006 Feb;24(1):17-24
pubmed: 16418974
J Biol Chem. 2002 Nov 1;277(44):41960-9
pubmed: 12185076
Nat Rev Genet. 2019 Apr;20(4):235-248
pubmed: 30647469
Eur J Hum Genet. 2004 Dec;12(12):985-6
pubmed: 15367916
Mol Hum Reprod. 2015 Apr;21(4):339-46
pubmed: 25504873
Genes Dev. 1998 Dec 1;12(23):3741-51
pubmed: 9851980
Eur J Hum Genet. 2003 Dec;11(12):972-4
pubmed: 14508508
Cell Chem Biol. 2019 Jan 17;26(1):121-130.e5
pubmed: 30472117