Embryo Developmental Arrest (EDA) is one of the mechanisms responsible for an increased level of embryo demise during the first week of in vitro development. Around 10-15% embryos permanently arrest in mitosis at the 2-to 4-cell cleavage stage. It involves the downregulation and/or cessation of cell division and metabolic activity of the components involved in the formation and development of an embryo. Chromosomal abnormalities, abnormal preimplantation development and single gene disorders have been stated as causes of EDA and therefore, a known cause of infertility. The identification of abnormal gene changes previously known to have an effect on embryo development is crucial to improve pregnancy outcomes.
The Igenomix Embryo Developmental Arrest Precision Panel can be used to make a directed and accurate differential diagnosis of inability to carry out a full pregnancy ultimately leading to a better management and achieve a healthy baby at home. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
The clinical utility of this panel is:
|
GENE |
OMIM DISEASES |
INHERITANCE* |
% GENE COVERAGE (20X) |
HGMD** |
|
BTG4 |
Zygotic Cleavage Failure, |
|
92.22% |
NA of NA |
|
C1QC |
C1q Deficiency |
AR |
100% |
11 of 11 |
|
CATSPER1 |
Spermatogenic |
AR |
99.97% |
4 of 4 |
|
CD46 |
HELLP Syndrome, |
AD,AR |
100% |
83 of 84 |
|
CNOT6L |
Embryo |
– |
98.92% |
NA of NA |
|
DMC1 |
Infertility |
– |
100% |
2 of 2 |
|
DNAH1 |
Primary Ciliary Dyskinesia, |
AR |
100% |
58 of 58 |
|
DNAH5 |
Primary Ciliary |
AR |
100% |
277 of 278 |
|
DPY19L2 |
Spermatogenic Failure |
AR |
97.65% |
16 of 20 |
|
EED |
Cohen-Gibson Syndrome, |
AD |
99.92% |
10 of 10 |
|
GALNTL5 |
Primary Infertility Due |
|
99.95% |
2 of 2 |
|
KHDC3L |
Recurrent Hydatidiform |
AR |
100% |
7 of 7 |
|
KLHL10 |
Male Infertility With |
AD |
99.98% |
5 of 5 |
|
NANOG |
Teratocarcinoma, |
|
97.74% |
NA of NA |
|
NANOS1 |
Male Infertility With |
AD |
75.55% |
2 of 3 |
|
NR5A1 |
46XX Gonadal Dysgenesis, |
AD |
99.97% |
222 of 224 |
|
PADI6 |
Preimplantation |
AR |
NA |
NA |
|
PICK1 |
Spermatogenic |
|
100% |
1 of 1 |
|
PLCZ1 |
Spermatogenic |
AR |
99.78% |
8 of 8 |
|
POU5F1 |
Embryonal Carcinoma, |
|
100% |
1 of 1 |
|
SEPTIN12 |
Spermatogenic Failure |
AD |
99.84% |
5 of 5 |
|
SLC26A8 |
Spermatogenic Failure |
AD |
98.81% |
5 of 5 |
|
SPATA16 |
Spermatogenic Failure |
AR |
99.94% |
1 of 2 |
|
SPP1 |
Pediatric Systemic |
|
99.77% |
2 of 2 |
|
STAT3 |
Acute Promyelocytic |
AD |
100% |
171 of 171 |
|
STK11 |
Pancreatic Cancer, |
AD |
81.99% |
456 of 470 |
|
SUN5 |
Male Infertility Due To |
AR |
100% |
14 of 14 |
|
SYCE1 |
Male Infertility With |
AR |
100% |
2 of 3 |
|
TAF4B |
Male Infertility With |
AR |
97.92% |
0 of 1 |
|
TERT |
Aplastic Anemia, |
AD,AR |
99.09% |
194 of 197 |
|
TEX11 |
Male Infertility With |
X,XR,G |
96.52% |
NA of NA |
|
TEX15 |
Male Infertility With |
AR |
99.16% |
6 of 7 |
|
TLE6 |
Preimplantation |
AR |
100% |
2 of 2 |
|
TUBB8 |
Oocyte Maturation |
AD,AR |
99.81% |
47 of 47 |
|
VSIG4 |
T-cell/Histiocyte |
– |
99.80% |
NA of NA |
|
ZFP42 |
Spermatocytoma, |
– |
99.98% |
NA of NA |
|
ZP1 |
Oocyte Maturation |
AR |
100% |
17 of 17 |
|
ZPBP |
Spermatogenic Failure |
|
99.98% |
4 of 4 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial; G: Gonosomal Inheritance; D: Digenic Inheritance
** HGMD: Number of clinically relevant mutations according to HGMD
Murphy, B. (2020). Under Arrest: The Embryo in Diapause. Developmental Cell, 52(2), 139-140. doi: 10.1016/j.devcel.2020.01.002
Levy, R. R., Cordonier, H., Czyba, J. C., & Guerin, J. F. (2001). Apoptosis in preimplantation mammalian embryo and genetics. Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia, 106(2 Suppl 2), 101–108.
Mohebi, M., & Ghafouri-Fard, S. (2019). Embryo developmental arrest: Review of genetic factors and pathways. Gene Reports, 17, 100479. doi: 10.1016/j.genrep.2019.100479
Zhang, X., Stojkovic, P., Przyborski, S., Cooke, M., Armstrong, L., Lako, M., & Stojkovic, M. (2006). Derivation of Human Embryonic Stem Cells from Developing and Arrested Embryos. Stem Cells, 24(12), 2669-2676. doi: 10.1634/stemcells.2006-0377
Sha, Q. Q., Zheng, W., Wu, Y. W., Li, S., Guo, L., Zhang, S., Lin, G., Ou, X. H., & Fan, H. Y. (2020). Dynamics and clinical relevance of maternal mRNA clearance during the oocyte-to-embryo transition in humans. Nature communications, 11(1), 4917. https://doi.org/10.1038/s41467-020-18680-6
Zhang, Y., Feng, Y., & Ma, F. (2020). Yi chuan = Hereditas, 42(10), 1004–1016. https://doi.org/10.16288/j.yczz.20-144
Feng, R., Yan, Z., Li, B., Yu, M., Sang, Q., Tian, G., Xu, Y., Chen, B., Qu, R., Sun, Z., Sun, X., Jin, L., He, L., Kuang, Y., Cowan, N. J., & Wang, L. (2016). Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos. Journal of medical genetics, 53(10), 662–671. https://doi.org/10.1136/jmedgenet-2016-103891
Xu, Y., Shi, Y., Fu, J., Yu, M., Feng, R., & Sang, Q. et al. (2016). Mutations in PADI6 Cause Female Infertility Characterized by Early Embryonic Arrest. The American Journal Of Human Genetics, 99(3), 744-752. doi: 10.1016/j.ajhg.2016.06.024
