A SPART missense mutation causes Troyer syndrome in two siblings

Abstract

Troyer syndrome, a rare autosomal-recessive disorder, manifests with complex spastic paraplegia. In Ohio, Amish families were the first to be reported with this syndrome. The neurological and musculoskeletal symptoms include short stature, dysarthria, distal amyotrophy, and spastic paralysis. A mutation in the SPGP20 gene, located on chromosome 13q13, results in the loss of the Spartin proteins, the source of pathogenicity. Spartin is a multifunctional protein thought to be crucial for neuron viability. Here, we report the clinical and molecular diagnostic findings of Troyer syndrome in two siblings from a consanguineous family in Saudi Arabia. The clinical phenotypes of the patients showed short stature and intellectual disability. The molecular genetic test, including whole-exome sequencing, was performed to identify and confirm the causative variant. A homozygous missense mutation in the SPART variant c.988A>G p.(Met330Val) was identified through molecular analysis. According to HGMD Professional 2021.1, this variant has previously been described as a disease-causing intellectual disability and Troyer syndrome.

Keywords

• hereditary spastic paraplegias
• intellectual disabilities
• short stature
• spg20
• troyer syndrome
• whole-exome sequencing