IVF, Embryo Screening Help SMA Carriers Have Healthy Baby
A combination of in vitro fertilization and preimplantation genetic testing helped a couple in Indonesia — both carriers of mutations causing spinal muscular atrophy (SMA) — become parents of a healthy newborn, a case study reported.
Their first daughter was diagnosed with SMA at 7 months, and she died of disease-related complications at 15 months old.
Preimplantation screening provides “a reliable genetic diagnostic method for SMA,” the researchers wrote, adding the case further supports its use for “genetically at-risk couples who are apprehensive about conceiving a child who might inherit monogenic [single-gene] disorders such as SMA.”
Genetic testing for SMA to potentially identify disease-free embryos
The case study, “Birth of spinal muscular atrophy unaffected baby from genetically at-risk parents following a pre-implantation genetic screening: A case report,” was published in the International Journal of Reproductive Medicine.
Nearly all SMA cases are caused by the complete loss of exon 7 in both copies of the SMN1 gene — one inherited from the mother and one from the father — so that little or no survival motor neuron (SMN) protein is produced. This protein is needed for motor neurons, the specialized nerve cells that regulate voluntary movement, and their loss leads to disease symptoms that can be marked at early ages by problems with movement and with speaking, swallowing and breathing difficulties.
The simultaneous loss of exons 7 and 8 also can be common. Exons are the sections of a gene that contain the information to generate proteins.
SMN2, a “backup” gene, can partly compensate for the loss of SMN1-produced SMN protein. People typically have at least two copies of this backup gene, with extra copies helping to produce more protein. Usually, the higher the number of SMN2 gene copies a patient has, the less severe is their disease.
People with a family member with SMA may ask to undergo genetic counseling to assess whether they carry an SMA-causing SMN1 mutation. If so, they are classified as carriers and can pass the condition to their children.
“Implementation of pre-implantation genetic testing for monogenic diseases (PGT-M) through in vitro fertilization (IVF) has become a promising conception strategy for couples who are at risk of passing on an abnormal gene to their child,” the researchers wrote.
During IVF, an egg is removed from a woman’s ovaries and fertilized with sperm in the lab. The fertilized egg, called an embryo, is then returned to the woman’s womb to grow and develop.
Preimplantation genetic testing can be performed on lab-grown embryos, so only those not carrying disease-causing mutations will be transferred to the womb.
A team of researchers in Jakarta described the case of a 26-year-old woman and 32-year-old man, both cousins, who carried a faulty SMN1 gene.
First child had exon 7 deletion in both SMN1 gene copies
After losing their first child, who had an exon 7 deletion in both SMN1 copies and two SMN2 gene copies, the couple visited a private clinic to seek an opinion about in vitro fertilization with preimplantation genetic screening (IVF-PGT-M) of the embryos. As SMA carriers, they had a 25% chance of having another baby with this disease.
“Geneticists and IVF specialists … took an important role during the counselling in which clear and comprehensive information concerning the possible risks and advantages of the program was given to the couple,” the researchers wrote.
“According to a survey study, the supply of clear information on the accuracy of [preimplantation genetic testing] served as one of the most important factors that determined the couples’ decision” to go ahead with the procedure, they added.
After initial IVF steps at the clinic, a total of 18 eggs were collected from the woman and fertilized in the lab with her husband’s sperm.
Three of these eggs developed into “top-quality” blastocysts, a developmental stage that looks like a ball of rapidly dividing embryonic cells. Two to four cells on each blastocyst were collected and sent for genetic analysis, and the embryos were frozen until ready to use.
Genetic testing for the loss of exon 7 and 8 in both SMN1 and SMN2 gene copies revealed that all three embryos carried healthy versions of the genes, “implying that the embryos were not affected by the SMN1-deletion type SMA,” the team wrote.
One of the embryos was thawed and transferred to the woman’s womb. Her pregnancy developed without complications and a healthy baby girl was born at 37 weeks of gestation. The infant showed normal activity and movements, muscle tone, and suckling reflex.
A genetic test given the baby at 21 days old confirmed the absence of any exon 7 or 8 deletions in the SMN1 or SMN2 gene, indicating that she “was not affected with the congenital SMA,” the researchers wrote.
The particular genetic testing approach used in this case “has a limitation in which the copy number of SMN1 and SMN2 genes could not be examined,” the researchers wrote, so that “the SMA carrier status of the baby could not be confirmed.”
But its lower costs may be of help to couples in developing countries, they added.
A program combining IVF and preimplantation genetic testing can help in being “a screening strategy to prevent conceiving a baby who would inherit SMA,” the team concluded.
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