Familial Prion Disease: First Indian Kindred with Gerstmann-Sträussler-Scheinker Syndrome

Gerstmann-Sträussler-Scheinker (GSS) syndrome is a devastating hereditary prion disease, presenting in 4th-5th decade with progressive ataxia and dementia. Pathogenic variants in the PRNP gene lead to aggregation of misfolded prion protein which results in neurodegeneration and death within a few years of onset. A key feature of prion disorders is conversion of normal prion protein (PrPc) into its misfolded form (PrPSc). Genetic modifiers include methionine at position 129 in prion protein and octapeptide repeats. We present an Indian kindred with c. 305C > T, p.Pro102Leu mutation in PRNP gene causing GSS in multiple members and discuss the impact of the polymorphism at position 129 on the severity of illness.