Two more families supporting the existence of monogenic spinocerebellar ataxia 48

• DOI: 10.1007/s10048-024-00758-8
• Publication Date: 2024-04-16T11:14:15Z
• Authors: Flavia Palombo; Alessandro Vaisfeld; Valentina Concett...; Danara Ormanbekova; Isabelle Bacchi; Claudio Fiorini; Adelaide Peruzzi; Luca Morandi; Rocco Liguori; Valerio Carelli; Giovanni Rizzo
• Keywords: Penetrance; Dysarthria; Cerebellar ataxia; Inheritance; Human genetics

The reduced penetrance of TBP intermediate alleles and the recently proposed possible digenic TBP/STUB1 inheritance raised questions on the possible mechanism involved opening a debate on the existence of SCA48 as a monogenic disorder. We here report clinical and genetic results of two apparently unrelated patients carrying the same STUB1 variant(c.244G > T;p.Asp82Tyr) with normal TBP alleles and a clinical picture fully resembling SCA48, including cerebellar ataxia, dysarthria and mild cognitive impairment. This report provides supportive evidence that this specific ataxia can also occur as a monogenic disease, considering classical TBP allelic ranges.