Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.

摘要: Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total 25 consanguineous families from Sudan. used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene was performed two other established genetic diagnosis six with autosomal recessive HSP (SPG11 three TFG/SPG57, SACS ALS2 one family each). A heterozygous mutation involved an dominant (ATL1/SPG3A) also identified additional family. Six out seven variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is that underlies HSP, we demonstrated its impact on TFG oligomerization vitro. Patients did not present visual impairment as observed previously reported SPG57 (c.316C>T (p.(Arg106Cys)) coiled-coil domain), suggesting unique contributions PB1 domains complex formation/function possible phenotype correlation location. Some manifested marked phenotypic variations implying possibility modifier factors complicated by high inbreeding. Finally, heterogeneity expected Sudanese remaining might unravel new or uncommon modes inheritance.