The SMN locus, located in humans in the 5q region, is the site of relative genomic copy number instability of two paralogous genes called SMN1 and SMN2. Deletion, balanced duplication or gene conversion are relatively frequent mutational events in this chromosomal region. While homozygous deletions of the SMN1 gene are well known to give rise to the classic infantile spinal amyotrophy (or SMA), the implication of such events in other motor neuron diseases remains controversial. Duplications of the SMN1 gene would thus be involved in certain forms of amyotrophic lateral sclerosis (ALS).
In an article published in June 2021, Dutch researchers looked for these duplications in several primary pathologies of the motor neuron including:
- multifocal motor neuropathy (MMN), an autoimmune disease sensitive to immunosuppressive treatments,
- progressive muscular atrophy (PMA: a variant of ALS with predominant involvement in the second motor neuron,
- and in progressive lateral sclerosis (PLS) another variant of ALS but with predominant involvement in the first motor neuron.
One hundred and thirty-two patients with MMN, 150 with PMA and 104 patients with PLS were explored and compared to 956 control subjects. The balanced duplications of SMN1 (3 copies and more) were found in the only PMA group suggesting a possible causal link between the two.
