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

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• Cerebellar atrophy and hypoplasia are observed in children with cerebellar ataxias, developmental delay, and intellectual disability.
• These neurological signs can be linked to hypo- or de-myelinating leukodystrophies.
• Previous reports suggested LSM7 as a candidate disease gene based on two cases with homozygous variants.

Purpose of the Study:

• To investigate the role of LSM7 gene variants in a patient presenting with neurodevelopmental defects, leukodystrophy, and cerebellar atrophy.
• To confirm the etiological link between LSM7 gene disruption and this specific neurodevelopmental disorder.

Main Methods:

• Clinical evaluation and neuroimaging (MRI) of the patient.
• Genetic analysis to identify variants in the LSM7 gene.
• Comparison with previously reported cases and functional data on LSM complex.

Main Results:

• The patient harbored compound heterozygous missense variants in the LSM7 gene.
• One identified variant was identical to a previously reported case; the other was at a functionally critical position.
• Clinical and neuroimaging findings were consistent with previously described LSM7-related disorders.

Conclusions:

• LSM7 gene disruption is confirmed to cause a neurodevelopmental disorder.
• The disorder is characterized by leukodystrophy and cerebellar atrophy.
• The findings support LSM7 as a significant genetic factor in pediatric neurological disorders.