Identification of a novel MAG gene mutation with 22q11.21 microduplication linked to hereditary spastic paraplegia

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Hereditary spastic paraplegia (HSP) diagnosis in children is challenging, frequently confused with cerebral palsy due to overlapping symptoms and non-specific neuroimaging.
• Absence of a family history and perinatal insult further complicates early and accurate diagnosis of HSP in pediatric cases.
• Genetic variants in the MAG gene (myelin-associated glycoprotein) are linked to complex forms of HSP.

Observation:

• A novel, apparently homozygous variant in the MAG gene (c.451del) was identified in a pediatric patient.
• This mutation leads to a frameshift and premature protein truncation, affecting myelin-associated glycoprotein function.
• The patient presented with cerebellar ataxia, nystagmus, and hypotonia, progressing to spastic paraplegia.

Findings:

• The identified MAG gene variant (c.451del) is pathologically significant and causative of HSP in the studied patient.
• This discovery highlights the role of MAG gene mutations in the pathogenesis of complicated HSP.
• The specific mutation results in a frameshift, leading to a non-functional myelin-associated glycoprotein.

Implications:

• Accurate genetic diagnosis of HSP, particularly in cases without a family history, can be achieved through identifying MAG gene variants.
• Early and correct diagnosis of pediatric HSP enables informed decisions regarding pregnancy and facilitates timely intervention strategies.
• Understanding the genetic basis of HSP aids in developing targeted therapies and improving patient management.