[Preimplantation genetic diagnosis in prevention of genetic diseases --diagnostic of spinal muscular atrophy (SMA)]. / Diagnostyka preimplantacyjna w zapobieganiu chorobom o podlozu genetycznym--diagnostyka rdzeniowego zaniku miesni (SMA--spinal muscular atrophy).

INTRODUCTION: Preimplantation genetic diagnosis, PGD, is an established procedure allowing genetic research of the oocyte or embryo before implantation to the uterus. A neurodegenerative disorder known as spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disease in Caucasians, after cystic fibrosis. There are three clinically different types of the disease, with type I (Werding-Hoffman Disease) being the most severe. Around 98% of clinical cases of SMA are caused by the homozygous absence of a region of exons 7 and 8 of the telomeric copy of the SMN gene (SMN1) on chromosome 5 (5q13.3). OBJECTIVES: The aim of the present work was to performed PGD for SMA in 5 couples who had already had a child affected with SMA. MATERIAL AND METHODS: All patients underwent a standard IVF procedure associated with intracytoplasmic sperm injection. 6-8 cell embryos were biopsied on day 3 of culture. Single cell nested PCR-RFLP protocol for PGD of SMA was used for the detection of the mutation. RESULTS: In the course of IVF-PGD procedures all patients had a transfer of embryos without SMN1 deletions. Four out of the five couples delivered healthy babies. CONCLUSIONS: Preimplantation genetic diagnosis (PGD) of monogenic disorders is a very efficient method, especially for patients whose previous child is homozygous for genetic disorders. It offers new possibilities for the treatment for genetic disease carriers.

Pregnancy and life after preimplantation genetic diagnosis of Smith-Lemli-Opitz syndrome.

OBJECTIVE: To use preimplantation genetic diagnosis to achieve Smith-Lemli-Opitz syndrome -free pregnancies in two couples at high risk of producing an affected child. DESIGN: Case report. SETTING: A private IVF unit. PATIENT(S): Two couples carrying the W151X mutation in the DHCR7 gene. INTERVENTION(S): Removal and testing for the W151X mutation in blastomeres from embryos after standard IVF. MAIN OUTCOME MEASURE(S): DNA analysis of blastomeres indicating whether corresponding embryos were mutation-free, for the purpose of transferring only unaffected embryos. RESULT(S): Delivery of healthy children without the W151X mutation in the DHCR7 gene. CONCLUSION(S): This is the first report of preimplantation genetic diagnosis for Smith-Lemli-Opitz syndrome, allowing transfer of mutation-free embryos and successful pregnancies.