| |
PGD for Single Gene Disorders
Single gene disorders
are genetic conditions caused by the alteration or mutation of
a specific gene in the affected person’s DNA. Single
gene disorders are inheritable and often run in families. Individuals
with a family history of a single gene disorder may be at risk for
passing the condition onto their children. Examples of single
gene disorders include cystic fibrosis, sickle cell anemia, Tay
Sachs disease, myotonic dystrophy, Duchenne and Becker muscular
dystrophies, Fragile X syndrome and spinal muscular atrophy,
to name a few.
What single gene disorders can be tested?
Below, we have listed the single gene disorders that
PGD has been attempted or successfully completed by our Institute.
If the disease you are interested in testing by PGD is not listed,
please contact us or
call 773-472-4900. In most cases, PGD is possible even for rare
genetic conditions, if the gene and/or gene change involved is
known.
In the Single Gene Disorders Tested listed
below we provided, where
possible, a link to a website with more information under "Disorder
Tested", a link to a medical website under "Link", an "X" to indicate
a "PGD Set up" is available, an "X" to
indicate a "PGD" and "Pregnancy" procedure is available, and an
"X" to
indicate a "Healthy Baby" was conceived.
How can PGD for single gene disorders help my family?
PGD is able to distinguish between genetically normal and affected embryos.
Currently, this is the only way to determine whether an embryo is unaffected with a
genetic condition prior to pregnancy. PGD has been utilized by many couples wishing to
greatly reduce the risk of having a child with a devastating genetic disorder.
How do we test for single gene disorders?
Generally, due to the limited amount of DNA that is available for
study (one cell) and due to the limited timeframe to obtain results,
a special system for testing will be developed for each couple, before
they begin their IVF cycle. This is called the PGD Setup. This often
requires a blood sample from each partner and may require additional
samples depending on the circumstances. Our genetic counselors will inform
you of the samples required, the time required for the PGD setup, and
the cost for the setup.
Once the setup is completed, PGD for single gene disorders can be performed
by:
There are two basic types of preimplantation diagnosis - polar body biopsy and
analysis and embryo biopsy and analysis. Both types of analysis have advantages
and limitations. Polar body testing focuses on the maternal contribution, and is
an earlier method of testing. Generally, polar body testing is performed in any
case where the female partner of the couple carries the gene of interest
(she may have the condition or she may be a carrier of that condition). Embryo
biopsy and analysis involves testing the embryo directly. Therefore, we can
analyze both maternal and paternal genetic contributions. Embryo biopsy is
performed in cases when the male partner carries the gene of interest (he may
have the condition or be a carrier of the condition). Embryo biopsy is performed
after the embryo has formed and in some cases has a higher chance of
misdiagnosis or error. In many cases, we analyze both polar body and embryo
cell (blastomere) in order to provide the highest level of accuracy possible.
Our genetic counselors will review with you which approach our Institute
believes to be the most beneficial to you.
The cell(s) that are biopsied (polar bodies and/or blastomeres) are analyzed
using a technique called polymerase chain reaction or PCR. PCR allows the laboratory
to use a small amount of DNA to obtain rapid and accurate results. In addition
to testing for the gene change(s) or mutation(s) running in the family, our
laboratory also will use DNA linked markers. Linked markers are used in a fashion
similar to DNA fingerprinting and allow the laboratory several ways to determine
which gene(s) have been inherited by each egg or embryo. We have found linked
markers to greatly increase the accuracy of PGD as well as increase the chances
to obtain a test result for each egg or embryo.
Intracytoplasmic sperm injection or ICSI is required when PGD is performed for single
gene disorders. ICSI is a technique in which a single sperm is injected directly
into each mature egg for the purpose of fertilization. ICSI was first introduced in
1990 as a fertility treatment for men with low sperm count or poor sperm quality.
Prior to ICSI, each egg was flooded with many sperm in order for one sperm to fertilize
the egg “naturally”. After fertilization, the remaining unused sperm (and sperm DNA)
surrounded the egg and developing embryo. When performing PGD for single gene
disorders, ICSI is required in order to greatly reduce the risk of sperm contamination
of the cells tested. Without the use of ICSI, the laboratory may incorrectly test the
excess sperm DNA, not the DNA from the egg or embryo, leading to misdiagnosis of the
embryo.
What is the accuracy of the testing?
Typically, the accuracy for polar body analysis is between 95-98% and the accuracy of
blastomere analysis (only) is between 90-98%. The accuracy of the testing will vary
depending upon the genetic condition being studied, the method by which it is being studied,
and the number of linked markers for the family. In addition, there will usually be a range
of different accuracies for each case, as there are several different possible outcomes. It
is important to keep in mind that the testing focuses in only on the condition being studied, a
nd it is not possible to check for all genetic and/or chromosome problems at this early stage of
embryo development.
Does PGD replace prenatal testing?
No, PGD does not replace prenatal testing, such as chorionic villus sampling or amniocentesis.
PGD is a research-based test allowing for a similar diagnosis to those available by prenatal testing.
However, prenatal testing is still recommended, as this is currently the standard-of-care. Our genetic
counselors can discuss what prenatal testing options are available to you.
Next Steps
Please review our PGD information packet and pamphets and contact our
genetic counselors at 773-472-4900 or e-mail
us with
any questions or inquiries
regarding our PGD program.
| Single Gene Disorder Tested |
Link |
Set Up |
PGD |
Pregnancy |
Baby |
| Achondroplasia |
MD |
X |
|
|
|
| Adenosine
Aminohydrolase (ADA) Deficiency |
MD |
X |
X |
|
|
| Adrenoleukodystrophy (X-Linked ALD) |
MD |
X |
X |
X |
X |
| Alpers Syndrome |
MD |
X |
|
|
|
| Alpha 1 Antitrypsin Deficiency |
MD |
X |
X |
|
|
| Alport
Syndrome |
MD |
X |
X |
|
|
| Aneuploidies by STR Genotyping |
MD |
X |
X |
X |
X |
| Angioedema, Hereditary |
MD |
X |
X |
|
|
| Ataxia-Telangiectasia
(AT) |
MD |
X |
X |
X |
X |
| Basal Cell Nevus Syndrome (Gorlin Syndrome) |
MD |
X |
X |
X |
X |
| Blepharophimosis, Ptosis, and Epicanthus Inversus (BPES) |
MD |
X |
X |
X |
X |
| Blood Group - Kell Cellano System |
MD |
X |
X |
X |
X |
| Brain Tumor, Posterior Fossa of Infancy, Familial |
MD |
X |
X |
|
|
| Canavan Disease |
MD |
X |
X |
|
|
| Ceriod Lipofuscinosis, Neuronal 2, LAE Infantile, CLN2 (Batten Disease) |
MD |
X |
X |
|
|
| Charcot-Marie-Tooth Disease Type 1A (CMT1A) |
MD |
X |
X |
X |
X |
| Charcot-Marie-Tooth Disease Type 1B (CMT1B) |
MD |
X |
X |
|
|
| Charcot-Marie-Tooth Disease, Axonal, Type 2E |
MD |
X |
X |
X |
X |
| Charcot-Marie-Tooth Disease, Type X-Linked, 1 (CMTX1) |
MD |
X |
X |
|
|
| Choroideremia (CHM) |
MD |
X |
X |
X |
X |
| Citrullinemia |
MD |
X |
X |
|
|
| Colon Cancer, Hereditary Nonpolyposis, Type1 |
MD |
X |
X |
X |
X |
| Congenital Adrenal Hyperplasia (CAH) |
MD |
X |
X |
X |
X |
| Connexin 26(Neurosensory Deafness) |
MD |
X |
X |
|
|
| Crouzon Syndrome (Craniofacial Dysostosis) |
MD |
X |
X |
X |
X |
| Currarino Triad |
MD |
X |
X |
X |
X |
| Cystic Fibrosis (CF) |
MD |
X |
X |
X |
X |
| Cystinosin (CTNS) |
MD |
X |
X |
|
|
| Darier-White Disease (DAR) |
MD |
X |
X |
X |
X |
| Diamond-Blackfan Anemia (and HLA) |
MD |
X |
X |
|
|
| Dyskeratosis Congenita, X-Linked |
MD |
X |
|
|
|
| Dystonia Torsion (DYT1) |
MD |
X |
X |
X |
X |
| Early-Onset Familial Alzheimer Disease |
MD |
X |
X |
X |
X |
| Ectodermal Dysplasia 1, Anhidrotic (ED1) |
MD |
X |
X |
|
|
| Ectodermal Dysplasia, Hypohidrotic (EDAR) |
MD |
X |
X |
X |
|
| Emery-Dreifuss Muscular Dystropy |
MD |
X |
X |
X |
X |
| Emery-Dreifuss Muscular Dystrophy, Autosomal Recessive (EDMD3) |
MD |
X |
X |
X |
X |
| Epidermolysis Bullosa Dystrophica, Pasini |
MD |
X |
X |
X |
|
| Epiphyseal Dysplasia, Multiple, 1 (EDM1) |
MD |
X |
X |
X |
|
| Exostoses, Multiple, Type 1 |
MD |
X |
X |
|
|
| Exudative Vitreoretinopathy, Familial, Autosomnal Dominant |
MD |
X |
|
|
|
| Fabry Disease |
MD |
X |
X |
X |
X |
| Facioscapulohumeral Muscular Dystrophy |
MD |
X |
X |
X |
|
| Familial Adenomatosis Polyposis |
MD |
X |
X |
X |
X |
| Familial Amyloid Polyneuropathy |
MD |
X |
X |
|
|
| Familial Dysautonomia (Riley-Day Syndrome, DYS) |
MD |
X |
X |
X |
X |
| Fanconi
Anemia A (and HLA) |
MD |
X |
X |
X |
X |
| Fanconi Anemia C (and HLA) |
MD |
X |
X |
X |
X |
| Fanconi Anemia F (and HLA) |
MD |
X |
X |
|
|
| Fanconi Anemia J (and HLA) |
MD |
X |
X |
|
|
| Fragile-X A Syndromes (FMR1) |
MD |
X |
X |
X |
X |
| Fragile-X E Syndromes |
MD |
X |
|
|
|
| Friederich Ataxia 1 (FRDA) |
MD |
X |
|
|
|
| Galactosemia |
MD |
X |
X |
|
|
| Gaucher Disease, Type 1 |
MD |
X |
X |
X |
X |
| Glycogen Storage Disease, Type VI |
MD |
X |
X |
|
|
| Hemophilia A |
MD |
X |
X |
X |
X |
| Hemophilia B |
MD |
X |
X |
X |
X |
| HLA Matching Genotyping |
MD |
X |
X |
X |
X |
| Holoprosencephaly |
MD |
X |
X |
X |
X |
| Hoyeraal-Hreidarsson Syndrome (HHS) |
MD |
X |
X |
X |
X |
| Hunter
Syndrome (Mucopolysaccharidosis II) |
MD |
X |
X |
X |
X |
| Huntington Chorea |
MD |
X |
X |
X |
X |
| Hurler Syndrome (Mucopolysaccharidosis IH) |
MD |
X |
X |
X |
X |
| Hydrocephalus, X-Linked (L1CAM) |
MD |
X |
X |
|
|
| Hypophosphatasia (Infantile) |
MD |
X |
X |
X |
|
| Immunodeficiency with Hyper-IgM, Type 1 |
MD |
X |
X |
X |
X |
| Incontinentia Pigmenti (IP) |
MD |
X |
X |
X |
X |
| Krabbe Disease |
MD |
X |
X |
X |
|
| Leukoencephalopathy with Vanishing White Matter |
MD |
X |
X |
|
|
| Li-Fraumeni Syndrome (Mutations in p53 Gene) |
MD |
X |
X |
X |
X |
| Long-Chain Hydroxyacyl-CoA Dehydrogenase (LCHAD) |
MD |
X |
X |
X |
X |
| Marfan Syndrome |
MD |
X |
X |
X |
X |
| Medium-Chain Hydroxylacyl-CoA Dehydrogenase (MCAD) |
MD |
X |
X |
|
|
| Metachromatic Luekodystropy |
MD
|
X |
|
|
|
| 5,10-@Methylenetetrahydrofolate Reductase (MTHFR) |
MD
|
X |
X |
|
|
| Microcoria-Congenital Nephrosis Syndrome |
MD |
X |
|
|
|
| Multiple Endocrine Neoplasia, 1(MEN1) |
MD |
X |
|
|
|
| Muscular Dystrophy, Duchenne Type (DMD) |
MD
|
X |
X |
X |
X |
| Muscular Dystrophy, Becker Type (BMD) |
MD
|
X |
X |
X |
X |
| Myotonic Dystrophy (DM1) |
MD
|
X |
X |
X |
X |
| Myotubular Myopathy 1 |
MD
|
X |
X |
X |
X |
| Neurofibromatosis Type 1 |
MD
|
X |
X |
X |
X |
| Neurofibromatosis Type 2 |
MD
|
X |
X |
X |
X |
| Norrie Disease |
MD
|
X |
X |
|
|
| Ocular Albinism, X-Linked |
MD
|
X |
X |
X |
|
| Oculocutaneous Albinism Type 1 |
MD
|
X |
X |
|
|
| Oculocutaneous Albinism Type 2 |
MD |
X |
X |
X |
X |
| Omenn Syndrome |
MD |
X |
X |
X |
X |
| Optic Atrophy |
MD
|
X |
X |
|
|
| Ornithine Carbamoyltransferase (OTC) Deficiency |
MD
|
X |
X |
X |
X |
| Osteogenesis Imperfecta |
MD
|
X |
X |
X |
X |
| Osteopetrosis, Malignant, Autosomal Recessive |
MD
|
X |
X |
|
|
| Pelizaes-Merzbacher Disease |
MD
|
X |
X |
X |
X |
| Phenylketonuria |
MD
|
X |
X |
X |
X |
| Polycystic Kidney Disease Autosomal Dominant Type 1 |
MD
|
X |
X |
X |
X |
| Polycystic Kidney Disease Autosomal Dominant Type 2 |
MD
|
X |
X |
X |
X |
| Polycystic Kidney Disease Autosomal Recessive ARPKD |
MD
|
X |
X |
X |
X |
| Popliteal Pterygium Syndrome |
MD
|
X |
X |
|
|
| Proprionic Acidemia |
MD |
X |
|
|
|
| Retinitis Pigmentosa |
MD
|
X |
X |
|
|
| Retinoblastoma |
MD
|
X |
X |
X |
X |
| Rett Syndrome |
MD |
X |
X |
|
|
| Rhesus Factor Compatibility (RH Factor) |
MD |
X |
|
|
|
| Sandhoff Disease |
MD
|
X |
X |
X |
X |
| Sickle Cell Anemia |
MD
|
X |
X |
X |
X |
| Smith-Lemli-Opitz Syndrome |
MD
|
X |
X |
|
|
| Spinal Muscular Atrophy (SMA) |
MD
|
X |
X |
X |
X |
| Spinocerebellar Ataxia Type 1 |
MD
|
X |
X |
X |
X |
| Spinocerebellar Ataxia Type 2 |
MD
|
X |
X |
X |
X |
| Spinocerebellar Ataxia Type 3, Machado-Joseph Disease (MJD) |
MD
|
X |
X |
X |
X |
| Spinocerebellar Ataxia Type 6 |
MD
|
X |
X |
|
|
| Spinocerebellar Ataxia Type 7 |
MD
|
X |
X |
|
|
| Stickler Syndrome |
MD
|
X |
X |
X |
|
| Succinic Semialdehyde Dehydrogenase Deficiency |
MD
|
X |
X |
X |
X |
| Symphalangism |
MD
|
X |
X |
X |
X |
| Tay-Sachs Disease (TSD) |
MD
|
X |
X |
X |
X |
| Thalassemia Alpha |
MD
|
X |
X |
X |
X |
| Thalassemia Beta |
MD
|
X |
X |
X |
X |
| Treacher Collins Syndrome |
MD
|
X |
X |
X |
X |
| Tuberous Sclerosis Type 1 |
MD
|
X |
X |
|
|
| Tuberous Sclerosis Type 2 |
MD
|
X |
X |
|
|
| Von Hippel-Lindau Syndrome (VHL) |
MD
|
X |
X |
X |
X |
| Wiscott Aldrich Syndrome |
MD |
X |
X |
|
|
| Zellweger Syndrome |
MD |
X |
X |
X |
X |
|