title: Preimplantation genetic testing for Marfan syndrome.
abstract: Marfan syndrome (MFS) is an autosomal dominant disease that affects the skeletal, ocular and cardiovascular systems. Defects in the gene that codes for fibrillin (FBN-1) are responsible for MFS. Here we report the world's first use of preimplantation genetic testing (PGT) to achieve a clinical pregnancy and live birth of a baby free of a Marfan mutation. One or two blastomeres from each embryo were tested for a CA repeat within the FBN-1 gene. The prospective mother is homozygous for the CA repeat (2/2) and has two normal copies of the FBN-1 gene, while the prospective father is heterozygous for the CA repeat (1/2), and is affected with the Marfan syndrome. In the father's family, allele 2 segregates with the mutated FBN-1 gene. For PGT, any embryo diagnosed as heterozygous for the CA repeat (1/2) would be presumed to have inherited normal FBN-1 genes from the father and the mother and be unaffected. One in-vitro fertilization (IVF) cycle yielded 12 embryos for preimplantation testing; six of the embryos were heterozygous for the CA repeat (1/2) and presumed to be free of the Marfan mutation. Five of the six embryos were subsequently transferred into the uterus. The fetus was tested by chorionic villus sampling and found to be free of the Marfan mutation by the same linkage analysis, had a normal fetal echocardiogram, and was normal at birth.
authors.affiliation: Genetics & IVF Institute, Fairfax, VA 22031, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Harton
authors.forename: P
authors.initials: P
authors.lastname: Tsipouras
authors.forename: M E
authors.initials: ME
authors.lastname: Sisson
authors.forename: K M
authors.initials: KM
authors.lastname: Starr
authors.forename: B S
authors.initials: BS
authors.lastname: Mahoney
authors.forename: E F
authors.initials: EF
authors.lastname: Fugger
authors.forename: J D
authors.initials: JD
authors.lastname: Schulman
authors.forename: M W
authors.initials: MW
authors.lastname: Kilpatrick
authors.forename: G
authors.initials: G
authors.lastname: Levinson
authors.forename: S H
authors.initials: SH
authors.lastname: Black
mesh_terms: D000328:Adult; D001483:Base Sequence; D001757:Blastomeres; D017931:DNA Primers / Q000235:genetics; D018900:Dinucleotide Repeats; D004624:Embryo Transfer; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D000071838:Fibrillin-1; D000071837:Fibrillins; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D054392:Adipokines
chemical_list: D017931:DNA Primers; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines