IVF in SPG3A HSP

Normal pregnancy achieved

From initially seeking genetic counselling, through gene testing, entry into an IVF program and four failed attempts, a 30-year-old woman with SPG3A finally achieved success with a normal pregnancy.

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.

SOURCE:  Adv Exp Med Biol. 2021;1339:341-345. doi: 10.1007/978-3-030-78787-5_42. PMID: 35023124 © 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.

Preimplantation Genetic Testing for Spastic Paraplegia Type 3

Christos Yapijakis  1   2   3 Iphigenia Gintoni  4   5 Costas Voumvourakis  6 George Chrousos  7

1. Unit of Orofacial Genetics, 1st Department of Pediatrics, National Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece. [email protected]

2. Laboratory of Molecular Genetics, Cephalogenetics Center, Athens, Greece. [email protected]

3. University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Choremion Laboratory, “Aghia Sophia” Children’s Hospital, Athens, Greece. [email protected]

4. Unit of Orofacial Genetics, 1st Department of Pediatrics, National Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece.

5. Laboratory of Molecular Genetics, Cephalogenetics Center, Athens, Greece.

6. 2nd Department of Neurology, National Kapodistrian University of Athens, Attikon Hospital, Athens, Greece.

7. University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Choremion Laboratory, “Aghia Sophia” Children’s Hospital, Athens, Greece.

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