Details

Autor(en) / Beteiligte

• van Swieten, John C.
• Brusse, Esther
• de Graaf, Bianca M.
• Krieger, Elmar
• van de Graaf, Raoul
• de Koning, Inge
• Maat-Kievit, Anneke
• Leegwater, Peter
• Dooijes, Dennis
• Oostra, Ben A.
• Heutink, Peter

Titel

A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia

Ist Teil von

• American journal of human genetics, 2003-01, Vol.72 (1), p.191-199

Ort / Verlag

Chicago, IL: Elsevier Inc

Erscheinungsjahr

2003

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Hereditary spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders for which ⩾14 different genetic loci have been identified. In some SCA types, expanded tri- or pentanucleotide repeats have been identified, and the length of these expansions correlates with the age at onset and with the severity of the clinical phenotype. In several other SCA types, no genetic defect has yet been identified. We describe a large, three-generation family with early-onset tremor, dyskinesia, and slowly progressive cerebellar ataxia, not associated with any of the known SCA loci, and a mutation in the fibroblast growth factor 14 ( FGF14) gene on chromosome 13q34. Our observations are in accordance with the occurrence of ataxia and paroxysmal dyskinesia in Fgf14-knockout mice. As indicated by protein modeling, the amino acid change from phenylalanine to serine at position 145 is predicted to reduce the stability of the protein. The present FGF14 mutation represents a novel gene defect involved in the neurodegeneration of cerebellum and basal ganglia.