PGD-ONE FM™

20
novators in Reproductive Genetics! PGD-ONE FM Preimplantation Diagnosis for Monogenic Diseases - most Frequent Mutations

Transcript of PGD-ONE FM™

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Innovators in Reproductive Genetics!

PGD-ONE FM™

Preimplantation Diagnosis for Monogenic Diseases - most Frequent Mutations

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Innovators in Reproductive Genetics!

Experience mattersJanuary 2005 – April 2015

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PGD ONE FM™ 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 5th/6th 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.

What is PGD ONE FM™?

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PGD ONE FM™ - Frequent Mutations

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

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PGD ONE FM™ - Frequent Mutations

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

174.999 156.450 (90%)

The Human Gene Mutation Database Mutation with PGD ONE FM™

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Mutation with PGD ONE FM™

Total number of entries for release 2015.3

HGMD

Missense/nonsense 97626Splicing 15990Regulatory 3297Small deletions 26113Small insertions 10927Small indels 2497Repeat variations 482Gross insertions/duplications 3182Complex rearrangements 1668Gross deletions 13217Total 174999PGD ONE FM™ 156450

90 % of all known mutations

Mutation type

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PGD ONE FM™

The most routinely sought point mutations in a PGD ONE FM™ preimplantation diagnosis

Traditional acc to HGVS Protein

F508del c.1521_1523delCTT p.Phe508del deletion 3

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

452G>A c.452G>A p.Trp151* substitution 1

- c.1054C>T p.Arg352Trp substitution 1

35delG c.35delG p.Gly12Valfs*2 deletion 1

IVS1+1G>A c.-23+1G>A - substitution 1

CFTR

DHCR7

GJB2

Cystic Fibrosis [219700]

Smith-Lemli-Opitz syndrome [270400])

Deafness [220290]

GeneName of the mutation

Type of the mutationMutation size

[nt] Disease

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PGD ONE FM™

Traditional acc to HGVS Protein

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.Ile1269Met*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 1Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase

deficiency 1 [604377]

- c.1277G>A p.Arg426His substitution 1

- c.1082G>T p.Gly361Val substitution 1ADSL Adenylosuccinate lyase deficiency [608222]

GeneName of the mutation

Type of the mutationMutation size

[nt] Disease

The most routinely sought point mutations in a PGD ONE FM™ preimplantation diagnosis

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PGD ONE FM™

Traditional acc to HGVS Protein

- c.3697G>C p. Ala1231Pro substitution 1

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]

- c.5131C>T p.Gln1711* substitution 1

- 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]

DMD Duchenne muscular dystrophy [310200]

CPS1 Carbamoylphosphate synthetase I deficiency [237300]

GeneName of the mutation

Type of the mutationMutation size

[nt] Disease

The most routinely sought point mutations in a PGD ONE FM™ preimplantation diagnosis

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• 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 PGS-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

Why is it worth to perform PGD ONE FM™?

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• 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

What are the indications for PGD ONE FM™?

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• Free PGD BIOPSY KIT™

• Free shipment• Online access to results

INVICTA Genetic Laboratory offers:

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Cooperation step by step

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Cooperation step by step cont.

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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.

NGS methodology

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Next Generation SequencingNGS used in the PGD ONE FM™ is currently the most up-to-date method of DNA analysis in the world. It provides exceptionally accurate, reliable and comprehensive results, from which it is possible to reduce the risk of monogenic diseases (most frequent mutations) in babies.

99,999%*

*NGS provides accuracy of 99.999% (Q50 quality assessment by Phred Quality Scores – indicator developed for evaluation of DNA sequence analysis methods).

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Next Generation Sequencing

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

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Literature1. 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.

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Literature cont. 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.

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INVICTA GENETICS Trzy Lipy 3, Gdansk 80-172 , PolandT. +48 58 58 58 804M. [email protected]. invictagenetics.com

About INVICTA GENETICSINVICTA is an experienced genetics laboratory (since 2000)

offering wide range PGD / PGS tests using state of art Next Generation Sequencing (NGS) techniques.