title: Successful preimplantation genetic diagnosis for sex Link Lesch--Nyhan Syndrome using specific diagnosis.
abstract: Lesch-Nyhan syndrome (LN) is a severe X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine phosphoribosyl transferase (HRT). Clinical features displayed by affected boys are particularly severe and disturbing and include hyperuricaemia, Characteristic neurological features including self-mutilation, choreothetosis, spasticity and mental retardation. A couple with a boy diagnosed with LN and a history of pregnancy termination was referred to the Hammersmith Hospital. Their affected son was born in 1982 after an uncomplicated pregnancy and vaginal delivery. Eight subsequent pregnancies had been unsuccessful. There were five therapeutic terminations and three spontaneous abortions, one at least directly caused by the sampling procedure during amniocentesis. From 1989 to 1991 two unsuccessful preimplantation genetic diagnosis (PGD) cycles by sexing were performed by DNA amplification. The mutation was characterized and a nested PCR protocol was designed which allowed the efficient amplification of the affected loci followed by the detection of the mutant allele by restriction digestion. Three PGD cycles were performed using this specific diagnostic test before a successful pregnancy was achieved resulting in the birth of a healthy unaffected baby girl.
authors.affiliation: Centre Génétique, U393 Instutut Necker, Hôpital des Enfants Malades,Paris, France.ray@necker.fr
authors.forename: P F
authors.initials: PF
authors.lastname: Ray
authors.forename: J C
authors.initials: JC
authors.lastname: Harper
authors.forename: A
authors.initials: A
authors.lastname: Ao
authors.forename: D M
authors.initials: DM
authors.lastname: Taylor
authors.forename: R M
authors.initials: RM
authors.lastname: Winston
authors.forename: M
authors.initials: M
authors.lastname: Hughes
authors.forename: A H
authors.initials: AH
authors.lastname: Handyside
mesh_terms: D004624:Embryo Transfer; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D008040:Genetic Linkage; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics; D007926:Lesch-Nyhan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis; D014960:X Chromosome
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase