Recurrent Pregnancy Loss – 14 genes
Infertility is defined as the failure to conceive, regardless of the cause, after 1 year of unprotected intercourse.
Overview
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Recurrent Pregnancy Loss (RPL) is one of the most common obstetric complications, affecting more than 30% of conceptions. These can occur during preimplantation, pre–embryonic, embryonic, early fetal, late fetal and stillbirth. An important number of losses are due to genetic abnormalities, nonetheless 50% of early pregnancy losses have been associated with chromosomal abnormalities. The majority are due to de novo non–disjunctional events during meiosis and balanced paternal translocations. Traditionally, the assessment of recurrent pregnancy loss was based on karyotyping techniques. However, advances in molecular genetic technology have provided an array of information regarding genetic causes and risk factors for pregnancy loss. One of the most innovative techniques with a significant role in RPL is preimplantation genetic testing in in vitro fertilization cycles.
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The Igenomix Recurrent Pregnancy Loss 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.
Indication
The Igenomix Recurrent Pregnancy Loss Precision Panel is indicated for those patients the following manifestations:
- Inability to conceive after 1 year of unprotected intercourse
- Family history of infertility
- Personal history of recurrent miscarriages
- Family history of recurrent miscarriages
- Previous failed IVF cycles
- Other failed assisted reproductive technology (ART) treatments
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team for an initial consultation, workup and assisted reproductive technologies (ART).
- Risk assessment of asymptomatic family members according to the mode of inheritance.
Genes & Diseases
See all genes & diseases
|
GENE |
OMIM DISEASES |
INHERITANCE* |
% GENE COVERAGE (20X) |
HGMD** |
|
CTNNA3 |
Familial Arrhythmogenic Right Ventricular Dysplasia |
AD |
99.97% |
14 of 17 |
|
DYNC2H1 |
Jeune Syndrome, Short Rib-Polydactyly Syndrome, Verma-Naumoff Type, Short-Rib Thoracic Dysplasia With Or Without Polydactyly |
AR,MU,D |
99.78% |
214 of 221 |
|
F2 |
Congenital Factor II Deficiency, Congenital Prothrombin Deficiency, Ischemic Stroke, Recurrent Pregnancy Loss, Venous Thromboembolism |
AD,AR,MU |
100% |
66 of 66 |
|
GLE1 |
Amyotrophic Lateral Sclerosis, Congenital Arthrogryposis With Anterior Horn Cell Disease, Lethal Congenital Contracture Syndrome |
AR |
100% |
17 of 17 |
|
ITGB3 |
Fetal And Neonatal Alloimmune Thrombocytopenia, Glanzmann Thrombasthenia |
AD,AR |
99.44% |
178 of 179 |
|
KCNH2 |
Familial Short QT Syndrome, Long Qt Syndrome, Romano-Ward Syndrome |
AD |
98.69% |
908 of 930 |
|
KCNQ1 |
Familial Atrial Fibrillation, Beckwith-Wiedemann Syndrome, Familial Short QT Syndrome, Jervell And Lange-Nielsen Syndrome, Long QT Syndrome, Romano-Ward Syndrome |
AD,AR |
93.23% |
600 of 624 |
|
KIF14 |
Autosomal Recessive Primary Microcephaly, Meckel Syndrome, Primary Microcephaly |
AR |
99.84% |
18 of 18 |
|
MECP2 |
Atypical Rett Syndrome, X-linked Autism, Severe Neonatal Encephalopathy Due To MECP2 Mutations, Lubs X-linked Mental Retardation Syndrome, Rett Syndrome, Trisomy Xq28,x-Linked Intellectual Disability-Psychosis-Macroorchidism Syndrome, X-linked Non-Syndromic Intellectual Disability |
X,XR,XD,MU,G |
99.81% |
NA of NA |
|
MTHFR |
Homocystinuria Due To Deficiency Of N(5,10)-Methylene Tetrahydrofolate Reductase Activity, Isolated Anencephaly, Isolated Exencephaly, Neural Tube Defects, Folate-Sensitive, Schizophrenia, Venous Thromboembolism |
AD,AR |
100% |
122 of 122 |
|
RYR1 |
Autosomal Dominant Centronuclear Myopathy, Autosomal Recessive Centronuclear Myopathy, Benign Samaritan Congenital Myopathy, Central Core Disease, Congenital Multicore Myopathy With External Ophthalmoplegia, Congenital Myopathy With Myasthenic-like Onset, Malignant Hyperthermia Of Anesthesia |
AD,AR |
97.63% |
733 of 746 |
|
SCN5A |
Familial Atrial Fibrillation, Brugada Syndrome, Dilated Cardiomyopathy, Familial Progressive Cardiac Conduction Defect, Long QT Syndrome, Progressive Familial Heart Block, Romano-Ward Syndrome, Sick Sinus Syndrome, Sudden Infant Death Syndrome, Ventricular Fibrillation |
AD,AR,MU |
99.45% |
929 of 942 |
|
SERPINE1 |
Plasminogen Activator Inhibitor-1 Deficiency |
AD,AR |
100% |
4 of 4 |
|
TIMP2 |
Conjuctivochalasis, Sorsby Fundus Dystrophy, Fibrosarcoma, Preterm Premature Rupture of the Membranes |
|
97.56% |
6 of 6 |
* 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
References
Page, J., & Silver, R. (2016). Genetic Causes Of Recurrent Pregnancy Loss. Clinical Obstetrics & Gynecology, 59(3), 498-508. Doi: 10.1097/Grf.0000000000000217
Crotti, L., Tester, D. J., White, W. M., Bartos, D. C., Insolia, R., Besana, A., Kunic, J. D., Will, M. L., Velasco, E. J., Bair, J. J., Ghidoni, A., Cetin, I., Van Dyke, D. L., Wick, M. J., Brost, B., Delisle, B. P., Facchinetti, F., George, A. L., Schwartz, P. J., & Ackerman, M. J. (2013). Long QT syndrome-associated mutations in intrauterine fetal death. JAMA, 309(14), 1473–1482. https://doi.org/10.1001/jama.2013.3219
Rajcan-Separovic E. (2020). Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. European journal of medical genetics, 63(2), 103644. https://doi.org/10.1016/j.ejmg.2019.04.001
Tur-Torres, M., Garrido-Gimenez, C., & Alijotas-Reig, J. (2017). Genetics of recurrent miscarriage and fetal loss. Best Practice & Research Clinical Obstetrics & Gynaecology, 42, 11-25. doi: 10.1016/j.bpobgyn.2017.03.007
Hyde, K. J., & Schust, D. J. (2015). Genetic considerations in recurrent pregnancy loss. Cold Spring Harbor perspectives in medicine, 5(3), a023119. https://doi.org/10.1101/cshperspect.a023119
Sultana, S., Nallari, P., & Ananthapur, V. (2020). Recurrent Pregnancy Loss (RPL): An overview. Journal Of Women’s Health And Development, 03(03). doi: 10.26502/fjwhd.2644-28840038
Popescu, F., Jaslow, C., & Kutteh, W. (2018). Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients. Human Reproduction, 33(4), 579-587. doi: 10.1093/humrep/dey021
