Preimplantation Genetic Testing for Spastic Paraplegia Type 3

Introduction: Spastic paraplegia type 3 (SPG3) is a common autosomal dominant neurogenetic disease, presenting during childhood with symptoms of mildly progressive spasticity and weakness of the lower limbs. SPG3 develops due to mutations of the ATL1 gene that encodes atlastin-1, a GTPase crucial for the function of dendrites of corticospinal neurons. Here we present a case of preimplantation genetic testing for SPG3.

Patient and methods: A 30-year-old woman with clinical symptoms of autosomal dominant spastic paraplegia since her first year of life asked for genetic counselling. DNA sequencing revealed the existence of mutation c.715C>T (p. R239C) in the ATL1 gene, confirming the diagnosis of SPG3. The patient asked for preimplantation testing for SPG3 after in vitro fertilization. An allele-specific method of PCR amplification was created in order to distinguish the mutant and the normal allele in the patient and her mother who also had SPG3, while her normal father served as control. The same nested PCR approach was used for the preimplantation testing of 11 available embryos.

Results: The presence of the c.715C>T (p. R239C) mutation in the ATL1 gene was found in five embryos while six embryos carried normal alleles and were selected for IVF implantation. After three failed gestation attempts and one pregnancy ended by a spontaneous miscarriage in the first trimester due to a chromosomal abnormality, there was an achieved pregnancy with a totally normal embryo.

Conclusion: SPG3 may be degrading to a patient's quality of life; therefore, appropriate genetic counselling and preimplantation molecular testing may be provided as an option of prevention in offspring.