Spastic Paraplegia 20 (Troyer Syndrome) via the SPART (SPG20) Gene

Spastic paraplegia 20 (SPG20) is a rare neurological disorder also known as Troyer syndrome. It is characterized by dysarthria, distal muscle wasting, delayed cognitive development, and paraparesis (Proukakis et al. 2004). Other symptoms have also been observed, such as choreoathetosis, anxiety, and skeletal abnormalities of the hand. SPG20 occurs with high frequency in the Amish population (Cross and McKusick 1967; Bakowska et al. 2008). It was also reported in a large Omani kindred (Manzini et al. 2010; Tawamie et al. 2015) and one Turkish family (Alazami et al. 2015). The onset is usually in early childhood.

The inheritance pattern of SPG20 in reported families is consistent with autosomal recessive inheritance. Pathogenic variants in SPART (SPG20) are causative for the disease (Patel et al. 2002). SPART encodes the protein Spartin, whose function is not fully understood. Spartin is thought to have roles in protein folding and turnover in mitochondria and endoplasmic reticulum (Milewska et al. 2009). The N-terminal MIT domain in Spartin is important for the interaction with microtubule and trafficking molecules (Ciccarelli et al. 2003).To date, only 3 pathogenic variants have been identified in SPART. In Amish patients with SPG20, a homozygous 1-bp deletion (c.1110delA) has been found (Patel et al. 2002; Bakowska et al. 2008). Manzini et al. (2010) identified a homozygous 2-bp deletion (c.364_365delAT) in an Omani kindred. Alazami et al. (2015) identified a homozygous 1-bp duplication (c.1450dupA) in a Turkish family.

It is difficult to estimate the clinical sensitivity of this test due to the lack of large cohort studies. All the pathogenic variants identified to date are detectable by this test.

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