The methylation patterns of the genes PAX6, HB9, CHAT, ARHGAP22, and SMN2 are different in cells from patients with spinal muscular atrophy (SMA) compared to those in healthy patients, according to a new study published in the journal Gene.

“This study clarifies the specificities of the disease pathogenesis and extends the knowledge of pathways involved in the SMA progression,” the authors wrote. It could constitute the basis to identify new potential targets to treat the disease.

SMA is caused by mutations in the SMN1 gene, which is the primary gene that encodes the survival motor neuron (SMN) protein, which is essential for the health of motor neurons. Some functional SMN protein is also made from a second gene in humans called SMN2. Researchers don’t understand why a decrease in SMN protein particularly affects motor neurons.

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In the present study, a team of researchers led by A.V. Kiselev, PhD, studied the methylation patterns of genes on different motor neuron differentiation stages in induced pluripotent stem cells from patients with SMA types 1 and 2 to identify factors that may be associated with the high clinical heterogeneity of the condition.

In particular, they assessed the methylation genes that play a role in pluripotency regulation, neural differentiation, and SMA development.

They found that 5 genes were differently methylated in SMA cells. It was already known that the methylation patterns of SMN2 and ARHGAP22 were different. This is the first report of an altered methylation pattern in the PAX6, HB9, and CHAT genes, which are essential for motor neuron differentiation and function.

“Altered expression of these genes due to their aberrant methylation may disturb the processes these genes regulate,” the researchers concluded.


Maretina MA, Valetdinova KR, Tsyganova NA, et al. Identification of specific gene methylation patterns during motor neuron differentiation from spinal muscular atrophy patient-derived iPSC. Gene. 2022;811(15):146109. doi:10.1016/j.gene.2021.146109