LSM7 variants involving key amino acids for LSM complex function cause a neurodevelopmental disorder with leukodystrophy and cerebellar atrophy.

Cerebellar atrophy and hypoplasia are usually identified on MRI performed on children presenting signs of cerebellar ataxias, developmental delay, and intellectual disability. These signs can be associated with hypo- or de-myelinating leukodystrophies. A recent study reported two cases: one child diagnosed with leukodystrophy and cerebellar atrophy, harboring a homozygous variant in LSM7, and another who died in utero, presumed to have another homozygous variant in LSM7, based on the parents' genotype. LSM7 encodes a subunit of the LSM complex, involved in pre-RNA maturation and mRNA degradation. Consequently, it has been suggested as a strong candidate disease gene. This hypothesis was supported by functional investigations of the variants. Here, we report a patient with neurodevelopmental defects, leukodystrophy, and cerebellar atrophy, harboring compound heterozygous missense variants in the LSM7 gene. One of these variants is the same as the one carried by the first case reported previously. The other one is at the same position as the variant potentially carried by the second case reported previously. Based on comparable neuroimaging, clinical features, and the involvement of the same amino acids previously demonstrated as key for LSM complex function, we confirm that LSM7 disruption causes a neurodevelopmental disorder characterized by leukodystrophy and cerebellar atrophy.