Preimplantation Diagnosis for Monogenic Diseases - most Frequent Mutations - PGD-ONE FM™

1. Innovators in Reproductive Genetics!
PGD-ONE FM
™
Preimplantation Diagnosis for Monogenic
Diseases - most Frequent Mutations

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Experience matters
January 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 97626
Splicing 15990
Regulatory 3297
Small deletions 26113
Small insertions 10927
Small indels 2497
Repeat variations 482
Gross insertions/duplications 3182
Complex rearrangements 1668
Gross deletions 13217
Total 174999
PGD 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

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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 1
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase
deficiency 1 [604377]
- c.1277G>A p.Arg426His substitution 1
- c.1082G>T p.Gly361Val substitution 1
ADSL Adenylosuccinate lyase deficiency [608222]
Gene
Name of the mutation
Type of the mutation
Mutation 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]
Gene
Name of the mutation
Type of the mutation
Mutation 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 Sequencing
NGS 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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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.

19. Innovators in Reproductive Genetics!
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 , Poland
T. +48 58 58 58 804
M. info@invictagenetics.com
W. invictagenetics.com
About INVICTA GENETICS
INVICTA is an experienced genetics laboratory (since 2000)
offering wide range PGD / PGS tests using state of art
Next Generation Sequencing (NGS) techniques.