Spastic Paraplegia 26 via the B4GALNT1 Gene

Spastic paraplegia 26 (SPG26) is a type of slowly progressive hereditary spastic paraplegia (HSP) characterized by spasticity and weakness of the lower limbs. SPG26 patients have an early onset (2-19 years old). The severity of symptoms is quite variable. Intellectual impairment is present in some SPG26 patients. About one third of SPG26 patients also have mild upper limb involvement (Boukhris et al. 2013). Other features include peripheral neuropathy, dystonia, dysarthria, cerebellar signs, cortical atrophy, urinary symptoms and extrapyramidal signs (Boukhris et al. 2013; Wakil et al. 2014).

The transmission pattern of SPG26 in the reported families is consistent with autosomal recessive (AR) inheritance. This disorder is caused by pathogenic variants in the B4GALNT1 gene (Wilkinson et al. 2005; Boukhris et al. 2013). To date, different types of pathogenic variants (missense, nonsense, splicing and in-frame and frameshift deletions/insertions) have been found in B4GALNT1 (Human Gene Mutation Database). B4GALNT1 encodes beta-1,4-N-acetyl-galactosaminyl transferase 1, which plays roles in ganglioside biosynthesis. Pathogenic variants in the B4GALNT1 gene impair the enzyme activity and cause the neurodegenerative phenotypes in SPG26 patients (Harlalka et al. 2013).

It is difficult to estimate the exact clinical sensitivity of this test due to the lack of large cohort studies. All the pathogenic variants in the B4GALNT1 gene reported to date can be detected by sequencing.

This test provides full coverage of all coding exons of the B4GALNT1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).