Spastic Paraplegia 56 via the CYP2U1 Gene

SPG56 is a type of hereditary spastic paraplegia (HSP) with complicated manifestations. This disorder is early onset, ranging from birth to 8 years (Citterio et al., 2014. PubMed ID: 24337409). The clinical features vary widely and age-dependent symptoms have been suggested (Iodice et al., 2017. PubMed ID: 28120039). The disease symptoms in the previously reported SPG56 cases include muscle stiffness, dystonia, motor regression, subclinical sensory motor neuropathy, intellectual disability and pigmentary degenerative maculopathy (Tesson et al., 2012. PubMed ID: 23176821; Kariminejad et al., 2016. PubMed ID: 27292318; Masciullo et al., 2016. PubMed ID: 26936192). Neuroimaging studies also found thin corpus callosum (TCC) and white matter alterations (WMA) in a few patients with this disorder (Tesson et al., 2012. PubMed ID: 23176821; Citterio et al., 2014. PubMed ID: 24337409).

SPG56 is inherited in an autosomal recessive (AR) manner. This disorder is caused by homozygous or compound heterozygous pathogenic variants in the CYP2U1 gene (Tesson et al., 2012. PubMed ID: 23176821). CYP2U1 catalyzes the hydroxylation of arachidonic acid and the related long-chain fatty acids. Previously studies suggest that CYP2U1 may play a role in the nervous and immune systems (Chuang et al., 2004. PubMed ID: 14660610). To date, different types of variants (missense, nonsense, splicing and frameshift deletions) have been found in CYP2U1 to cause SPG56 (Human Gene Mutation Database).

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 CYP2U1 gene reported to date can be detected by sequencing.

This test provides full coverage of all coding exons of the CYP2U1 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).