BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is ≥43. OBJECTIVE: To investigate the minimal CAG/CAA expansion within the TBP in SCA17. RESULTS: 285 patients with autosomal-dominant ataxia were examined, and abnormal or borderline expansions of CAG/CAA within TBP in eight cases were found. Of those, four patients from three families had exactly 42 CAG/CAA trinucleotides, that is, one codon less than the currently accepted critical threshold of 43. The four patients presented with a relatively benign phenotype. All had dysdiadochokinesia and dysarthria. Mild gait ataxia was observed in three of the four patients. CONCLUSION: The reference definition of at least 43 CAG/CAA codons for pathological SCA17 alleles should be lowered to 42.
BACKGROUND:Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is ≥43. OBJECTIVE: To investigate the minimal CAG/CAA expansion within the TBP in SCA17. RESULTS: 285 patients with autosomal-dominant ataxia were examined, and abnormal or borderline expansions of CAG/CAA within TBP in eight cases were found. Of those, four patients from three families had exactly 42 CAG/CAA trinucleotides, that is, one codon less than the currently accepted critical threshold of 43. The four patients presented with a relatively benign phenotype. All had dysdiadochokinesia and dysarthria. Mild gait ataxia was observed in three of the four patients. CONCLUSION: The reference definition of at least 43 CAG/CAA codons for pathological SCA17 alleles should be lowered to 42.
Authors: David N Cooper; Michael Krawczak; Constantin Polychronakos; Chris Tyler-Smith; Hildegard Kehrer-Sawatzki Journal: Hum Genet Date: 2013-07-03 Impact factor: 4.132
Authors: Suran Nethisinghe; Wei N Lim; Heather Ging; Anna Zeitlberger; Rosella Abeti; Sally Pemble; Mary G Sweeney; Robyn Labrum; Charisse Cervera; Henry Houlden; Elisabeth Rosser; Patricia Limousin; Angus Kennedy; Michael P Lunn; Kailash P Bhatia; Nicholas W Wood; John Hardy; James M Polke; Liana Veneziano; Alfredo Brusco; Mary B Davis; Paola Giunti Journal: Front Cell Neurosci Date: 2018-11-23 Impact factor: 5.505