Successful preimplantation genetic diagnosis for sex linked Lesch-Nyhan syndrome using specific diagnosis

Lesch-Nyhan syndrome (LN) is a severe X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine phosphoribosyl transferase (HPRT). Clinical features displayed by affected boys are particularly severe and d isturbing and include hyperuricaemia, characteristic neurological features including self-mutilation, choreothetosis, spasticity and mental retardatio n. A couple with an boy diagnosed with LN and a history of pregnancy termin ation was referred to the Hammersmith Hospital. Their affected son was born in 1982 after an uncomplicated pregnancy and vaginal delivery. Eight subse quent pregnancies had been unsuccessful. There were five therapeutic termin ations and three spontaneous abortions, one at least directly caused by the sampling procedure during amniocentesis. From 1989 to 1991 two unsuccessfu l preimplantation genetic diagnosis (PGD) cycles by sexing were performed b y DNA amplification. The mutation was characterized and a nested PCR protoc ol was designed which allowed the efficient amplification of the affected l oci followed by the detection of the mutant allele by restriction digestion . Three PGD cycles were performed using this specific diagnostic test befor e a successful pregnancy was achieved resulting in the birth of a healthy u naffected baby girl. Copyright (C) 1999 John Wiley & Sons, Ltd.