PREGNANCY AFTER PREIMPLANTATION GENETIC DIAGNOSIS FOR CHARCOT-MARIE-TOOTH-DISEASE TYPE 1A

Charcot-Marie-Tooth (CMT) disease type 1A is an autosomal dominant per ipheral neuropathy characterized by slow progressive distal muscle was ting and weakness, and decreased nerve conduction velocities. Most CMT 1A cases (>98%) are caused by a duplication of a 1.5 Mb region on the short arm of chromosome 17 containing the PMP22 gene. A couple with a previous history of CMT followed by termination of pregnancy was refer red to our centre for preimplantation genetic diagnosis (PGD). The hus band carries the CMT1A duplication which can be detected by polymerase chain reaction (PCR) analysis using polymorphic (CA), markers localiz ed within the duplication. PCR amplification of genomic DNA of the par ents-to-be with one of the two primers labelled with fluorescein, foll owed by automated laser fluorescence (ALF) gel electrophoresis of the amplified fragments allows the distinction between both genotypes. Emb ryos obtained after intracytoplasmic sperm injection (ICSI) were evalu ated for the presence of the normal allele of the father. PCR with sin gle Epstein-Barr virus-transformed lymphoblasts and blastomeres result ed in 91.4 and 93.5% amplification efficiency respectively, whereas no ne of the blank controls gave a positive signal. Allele drop-out (ADO) was observed in eight out of 32 lymphoblasts (25%) or in five out of 21 blastomeres (23.8%). However, within this set-up ADO will never lea d to transfer of an affected embryo. A first ICSI-PGD cycle did not re sult in embryo transfer for the patient. A second cycle involved 10 ma ture oocytes of which eight were fertilized, resulting in five embryos for biopsy. Two unaffected embryos were available for transfer and re sulted in a singleton pregnancy. The genotype of the fetus has been co nfirmed healthy by chorionic villus sampling.