EnglishHotline:
PGD ONE FM™
PGDA NGS for monogenic diseases
– most frequent mutations
What is PGD ONE FM™?
PGD ONE™ is a test that detects the genetic defects (most frequent mutations) inherited by a child from their parents. DNA material from embryos is analysed prior to transfer to the uterus, that is, before the woman actually becomes pregnant.
The test can be carried out on material collected by biopsy in the 3rd (blastomere) or 5th/6th (trophectoderm cells) day of the embryo culture. Because of the risk of misdiagnosis caused by the pollution of sperm when using standard in vitro fertilization, the ICSI procedure is recommended. Any diagnosis of PGD ONE FM™ is treated individually and preceded by an examination of the material from the prospective parents. Under the procedure, a frozen embryos transfer (FET) is required.
We offer testing for all changes (mutations) in the nucleotide sequence such as:
- single-nucleotide substitutions
- deletions – up to 20 nucleotides
- insertions – up to 20 nucleotides
The world’s first use of NGS (Next Generation Sequencing) in the
PGD ONE FM™ preimplantation diagnosis for monogenic diseases.
INVICTA Genetic Laboratory: February 2015
Based on the current HGMD database (The Human Gene Mutation Database) - With PGD ONE FM™ we can perform diagnostic tests for almost 90% of all known mutations:
170.118
The Human Gene Mutation Database
152.085
Mutation with PGD ONE FM™ (90% of all known mutations)
Why is it worth to perform PGD ONE FM™?
- Possibility of diagnosing known genetic-based monogenic disease (most frequent mutations) at the embryo stage, and reducing the risk of its occurrence in your child
- Possibility of conducting a PGDA NGS 360°™ (Preimplantation Genetic Screening) from a single sample (single biopsy) at the same time – reducing the risk of monogenic diseases (most frequent mutations) and genetic defects resulting from an abnormal number of chromosomes
Table 1. The most routinely sought point mutations in a PGD ONE FM™ preimplantation diagnosis
| Gene | Name of the mutation | Type of the mutation | Mutation size | Disease | ||
|---|---|---|---|---|---|---|
| Traditional | acc to HGVS | Protein | ||||
| CFTR | F508del | c.1521_1523delCTT | p.Phe508del | deletion | 3 | Cystic Fibrosis [219700] |
| R117H | c.350G>A | p.Arg117His | substitution | 1 | ||
| 3600+2insT | c.3468+2dupT | - | duplication | 1 | ||
| 1717-1G>A | c.1585-1G>A | - | substitution | 1 | ||
| R347P | c.1040G>C | p.Arg347Pro | substitution | 1 | ||
| 2184delA | c.2052delA | p.Lys684Asnfs*38 | deletion | 1 | ||
| 2184insA | c.2052_2053insA | p.Gln685Thrfs*4 | insertion | 1 | ||
| DHCR7 | 452G>A | c.452G>A | p.Trp151* | substitution | 1 | Smith-Lemli-Opitz syndrome [270400]) |
| - | c.1054C>T | p.Arg352Trp | substitution | 1 | ||
| GJB2 | 35delG | c.35delG | p.Gly12Valfs*2 | deletion | 1 | Deafness [220290] |
| IVS1+1G>A | c.-23+1G>A | - | substitution | 1 | ||
| NBN | 657del5 | c.657_661delACAAA | p.Lys219Asnfs*16 | deletion | 5 | Nijmegen breakage syndrome [251260] |
| TSC1 | 2332delAT | c.2111_2112delAT | p.Tyr704* | deletion | 2 | Tuberous sclerosis complex [191100] |
| WAS | c.325_334del10bp | c.325_334del10 | p.Ser108fs*16 | deletion | 10 | Wiskott-Aldrich syndrome [301000] |
| APC | - | c3807_c.3808delAT | p.lle1269Met*fs6 | deletion | 2 | Familial Adenomatous Polyposis, FAP [175100] |
| KRT14 | - | c.374G>A | p.Arg125His | substitution | 1 | Epidermolysis bullosa simplex, EB [175100] |
| PMM2 | - | c.385G>A | p.Val129Met | substitution | 1 | Congenital disorder of glycosylation type Ia [212065] |
| COL1A1 | - | c.2155G>T | p.Gly719Cys | substitution | 1 | Osteogenesis imperfecta, OI [166200] |
| ASL | - | c.337C>T | p.Arg113Trp | substitution | 1 | Argininosuccini caciduria, AS [207900] |
| PROP1 | c.301delAG | c.301_302delAG | p.Leu102Cysfs*8 | deletion | 2 | Pituitary hormone deficiency, combined, 2; CPHD2 [262600] |
| SCO2 | G1541A | c.418G>A | p.Glu140Lys | substitution | 1 | Cardioencephalomyopathy, fatal infatile, due to cytochrome c oxidase deficiency 1 [604377] |
| ADSL | - | c.1277G>A | p.Arg426His | substitution | 1 | Adenylosuccinate lyase deficiency [608222] |
| - | c.1082G>T | p.Gly361Val | substitution | 1 | ||
| CPS1 | - | c.3697G>C | p.Ala1231Pro | substitution | 1 | Carbamoylphosphate synthetase I deficiency [237300] |
| IVS16-8A>G | c.1836-8A>G | - | substitution | 1 | ||
| NBS1 | 657del5 | c.657_661delACAAA | p.Lys219Asnfs*16 | deletion | 5 | Nijmegen breakage syndrome, NBS [251260] |
| LDLR | - | c.935_936delAG | p.Glu312Valfs*19 | deletion | 2 | Hypercholesterolemia, familial [143890] |
| F8 | - | c.530_540del10 | p.Tyr177Cysfs*18 | deletion | 10 | Hemophilia A;HEMA [306700] |
| DMD | - | c.5131C>T | p.Gln1711* | substitution | 1 | Duchenne muscular dystrophy [310200] |
| - | c.6554dupT | p.Leu2185Phefs*38 | duplication | 1 | ||
| HBB | - | c.20A>T | p.Glu7Val | substitution | 1 | Sickle cell anemia [603903] |
| HBB | - | c.27dupG | p.Ser10Valfs*14 | duplication | 1 | Thalassaemia beta [613985] |
What are the indications for PGD ONE FM™?
- People with a genetic test result confirming a clinical diagnosis of monogenic disease (most frequent mutation)
- People with a genetic test result confirming the presence of mutation carriers
- The presence of inherited genetic diseases or a history of specific mutation in the family
INVICTA Genetic Laboratory provides:
- Specialist Collection Kit INVICTA PGD BIOPSY KIT™
- Free transport
- Online access to the results
Limitations
PGD ONE FM™ is individually designed preimplantation genetic diagnosis for particular patients in order to exclude transmission to descendant a genetic feature proven to be a cause of disease by test results from genetic diagnostics laboratory. Performing PGD ONE FM™ does not exclude risk of genetic disease, which may be resulted from other factors, e.g. de novo mutations, undiagnosed mutations, or other genetic diseases.
Literature
- 1. Lukaszuk K, Kalwak K, Pukszta S, Liss J, Jakiel G, Woclawek-Potocka I, Galvao A, Wasniewski T. Preimplantation genetic diagnosis of human leukocyte antigen for X-linked immunoproliferative syndrome caused by SAP mutation.
- 2. Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:252-3. doi: 10.1016/j. ejogrb.2014.09.034. Epub 2014 Sep 28.
- 3. Treff NR, Fedick A, Tao X, [et.al.]. Evaluation of targeted next-generation sequencing-based preimplantation genetic diagnosis of monogenic disease. Fertil Steril. 2013, 99(5),1377-1384.
- 4.Corrales I, Catarino S, Ayats J, Arteta D, Altisent C, Parra R, et al. High-throughput molecular diagnosis of von Willebrand disease by next generation sequencing methods. Haematologica 2012;97:1003.
- 5. Rechitsky S, Pakhalchuk T, San Ramos G, Goodman A, Zlatopolsky Z, Kuliev A.First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing. Fertil Steril. 2015 Feb;103(2):503-12. doi: 10.1016/j.fertnstert.2014.11.007. Epub 2014 Dec 13.
- 6. Berger VK, Baker VL. Preimplantation diagnosis for single gene disorders. Semen Reprod Med. 2014 Mar;32(2):107-13. doi: 10.1055/s-0033-1363552. Epub 2014 Feb 10.
- 7. Daina G, Ramos L, Obradors A, Rius M, Martinez-Pasarell O, Polo A, Del Rey J, Obradors J, Benet J, Navarro J. First successful double-factor PGD for Lynch syndrome: monogenic analysis and comprehensive aneuploidy screening. Clin Genet. 2013 Jul;84(1):70-3. doi: 10.1111/cge.12025. Epub 2012 Oct 17.
- 8. Chang LJ, Chen SU, Tsai YY, Hung CC, Fang MY, Su YN, Yang YS. An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening. Clin Exp Reprod Med. 2011 Sep;38(3):126-34. doi: 10.5653/cerm.2011.38.3.126. Epub 2011 Sep 30.
- 9. Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, Pehlivan Budak T, Renwick P, De Rycke M, Geraedts JP, Harton G. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012 May- Jun;18(3):234-47. doi: 10.1093/humupd/dmr052. Epub 2012 Feb 16. Review.
- 10. Field PD, Martin NJ. CFTR mutation screening in an assisted reproductive clinic. Aust N Z J Obstet Gynaecol. 2011 Dec;51(6):536-9. doi: 10.1111/j.1479- 828X.2011.01348.x. Epub 2011 Aug 22.
- 11. Preimplantation genetic diagnosis: state of the art 2011. Harper JC, Sengupta SB. Hum Genet. 2012 Feb;131(2):175-86. doi: 10.1007/s00439-011-1056-z. Epub 2011 Jul 12. Review.
- 12. Peyvandi F, Garagiola I, Mortarino M.Prenatal diagnosis and preimplantation genetic diagnosis: novel technologies and state of the art of PGD in different regions of the world. Haemophilia. 2011 Jul;17 Suppl 1:14-7. doi: 10.1111/j.1365- 2516.2011.02559.x
- 13. Simpson JL. Preimplantation genetic diagnosis at 20 years. Prenat Diagn. 2010 Jul;30(7):682-95. doi: 10.1002/pd.2552. Review.
- 14. Basille C, Frydman R, El Aly A, Hesters L, Fanchin R, Tachdjian G, Steffann J, LeLorc’h M, Achour-Frydman N. Preimplantation genetic diagnosis: state of the art. Eur J Obstet Gynecol Reprod Biol. 2009 Jul;145(1):9-13. doi: 10.1016/j. ejogrb.2009.04.004. Epub 2009 May 2.
- 15. Gutiérrez-Mateo C, Sánchez-García JF, Fischer J, Tormasi S, Cohen J, Munné S, Wells D. Preimplantation genetic diagnosis of single-gene disorders: experience with more than 200 cycles conducted by a reference laboratory in the United States. Fertil Steril. 2009 Nov;92(5):1544-56. doi: 10.1016/j.fertnstert.2008.08.111. Epub 2008 Oct 19.