Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan - Sorbonne Université Access content directly
Journal Articles European Journal of Human Genetics Year : 2016

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

Hassab Elrasoul S A Mohamed
  • Function : Author
Mahmoud Koko
Hanan Eltahir
  • Function : Author
Nasr Aldin A Magboul
  • Function : Author
Abdelrahman Elnour
  • Function : Author
Abdelmoneim Alattaya
  • Function : Author
Anjon Audhya
  • Function : Author

Abstract

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

Dates and versions

hal-04592584 , version 1 (29-05-2024)

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Liena Elsayed, Inaam Mohammed, Ahlam Hamed, Maha Elseed, Adam Johnson, et al.. Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan. European Journal of Human Genetics, 2016, 25 (1), pp.100-110. ⟨10.1038/ejhg.2016.108⟩. ⟨hal-04592584⟩
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