Brain Advance Access published online on May 6, 2003
Brain, doi:10.1093/brain/awg155
© 2003 by Guarantors of Brain
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Article
1 INSERM U289, Hôpital de la Salpêtrière, Paris, France; Institut Fédératif des Neurosciences, Paris, France
* Corresponding author. E-mail: brice{at}ccr.jussieu.fr.
Received 17 January 2003
; revised 24 January 2003
; accepted 24 February 2003
We report a group of 252 patients with a Huntington's disease-like (HDL) phenotype, including 60 with typical Huntington's disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington's disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington's disease. Taking into account patients with typical Huntington's disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
Keywords: Huntington's disease; junctophilin-3; spinocerebellar ataxia 17; TBP; Huntington's disease-like phenotype
Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes
2 INSERM U289, Hôpital de la Salpêtrière, Paris, France; Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan
3 INSERM U289, Hôpital de la Salpêtrière, Paris, France; Institut Fédératif des Neurosciences, Paris, France; Département de Génétique, Cytogénétique et Embryologie, Paris, France
4 INSERM U289, Hôpital de la Salpêtrière, Paris, France
5 Laboratoire de Biochimie et de Génétique Moléculaire, Groupe Hospitalier Cochin Port-Royal AP-HP, Paris, France
6 INSERM U106, Groupe Hospitalier Pitié-Salpêtrière AP-HP, Paris, France; Division of Neuropathology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
7 Unité de Neuromyologie, Hôpital Pierre Zobda-Quitman, CHU de Fort-de-France, Martinique, French West Indies
8 INSERM U289, Hôpital de la Salpêtrière, Paris, France; Institut Fédératif des Neurosciences, Paris, France; Département de Génétique, Cytogénétique et Embryologie, Paris, France; Fédération de Neurologie, Paris, France
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