title: Birth of healthy female twins after preimplantation genetic diagnosis of cystic fibrosis combined with gender determination.
abstract: Two healthy sisters with a familial history of mental retardation were referred to our centre for preimplantation genetic diagnosis (PGD). Their two brothers showed severe mental retardation. The molecular basis for their disorder could not be identified, but one of the sisters and the mother presented a highly skewed pattern of X-inactivation reinforcing the likelihood of an X-linked mode of inheritance. Both sisters requested PGD to avoid the abortion of potentially affected male fetuses. PGD for sex by fluorescent in-situ hybridization was carried out for the first sister and resulted in the birth of a female child. The second sister and her partner, whose niece had cystic fibrosis (CF), were tested for CF mutations, and were both found to be deltaF508 heterozygous. We developed an efficient single cell PCR protocol for the simultaneous amplification of the CF (deltadeltaF508) locus as well as the X-linked amelogenin gene and its highly homologous pseudogene on the Y chromosome. Two PGD cycles were carried out to screen against male and deltaF508 homozygous deleted embryos. In each case several embryos could be selected for transfer and the second cycle resulted in a twin pregnancy followed by the birth of two healthy female infants.
authors.affiliation: Département de Génétique, U393, IRNEM, Hôpital Necker Enfants Malades, 75743 Paris Cedex 15, France. ray@necker.fr
authors.forename: Pierre F
authors.initials: PF
authors.lastname: Ray
authors.forename: Nelly
authors.initials: N
authors.lastname: Frydman
authors.forename: Tania
authors.initials: T
authors.lastname: Attié
authors.forename: Samir
authors.initials: S
authors.lastname: Hamamah
authors.forename: Violaine
authors.initials: V
authors.lastname: Kerbrat
authors.forename: Gérard
authors.initials: G
authors.lastname: Tachdjian
authors.forename: Serge
authors.initials: S
authors.lastname: Romana
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: René
authors.initials: R
authors.lastname: Frydman
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000517:prevention & control; D010375:Pedigree; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D012743:Sex Preselection; D014429:Twins, Dizygotic