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

Diagnosing hereditary spastic paraplegia (HSP) in paediatric patients can be challenging, especially when there is no positive family history. Children are often initially misdiagnosed with cerebral palsy due to the gradual progression of the disease and non-specific neuroimaging findings, despite the absence of perinatal insult. This misdiagnosis can prevent timely prenatal diagnosis, limiting the ability to make informed decisions about the pregnancy and to plan early interventions. Homozygous variants in the MAG gene, encoding myelin-associated glycoprotein (MAG), have been associated with complicated forms of HSP. In this study, we identified a novel mutation suggestive of an apparently homozygous variant of the MAG gene with deletion in exon 5 (c.451del (p.Ala151GlnfsTer22)) that is predicted to result in a frameshift and premature truncation of the protein 22 amino acids downstream to codon 151. This variant was of pathological significance in our patient who presented with cerebellar ataxia, nystagmus and hypotonia, gradually progressing to spastic paraplegia. Therefore, identifying these variants helps in understanding the underlying genetic factors contributing to HSP, aiding in correct diagnosis.